Melanoma
Conditions
Keywords
Melanoma, Cutaneous melanoma, Skin disease, Skin cancer, Skin Neoplasms, Neoplasm Metastasis, BRAF mutant, BRAF V600E, BRAF V600K, Cancer, LGX818, MEK162, vemurafenib, combination, BRAF inhibitor, resistance, The combination of a selective BRAF- and a MEK1/2-inhibitor, Prior immunotherapy, MEK inhibitor, Phase III, Combo 300, Combo 450
Brief summary
This is 2-part, randomized, open label, multi-center, parallel group, phase III study comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818 monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. A total of approximately 900 patients will be randomized. Part 1: Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms: 1. LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm) 2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or 3. vemurafenib 960 mg BID (denoted as vemurafenib arm) Part 2: Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms: 1. LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or 2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm)
Interventions
DRUGLGX818
LGX818- Orally 100 mg and 50 mg capsules
DRUGMEK162
MEK162- Orally 15 mg tablets
DRUGvemurafenib
Tablets in bottles or blisters 240 mg
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV) * Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization * Naïve untreated patients or patients who have progressed on or after prior first line immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy or chemotherapy), except the administration of BRAF or MEK inhibitors * Evidence of at least one measurable lesion as detected by radiological or photographic methods * ECOG performance status of 0 or 1 * Adequate bone marrow, organ function, cardiac and laboratory parameters * Normal functioning of daily living activities
Exclusion criteria
* Any untreated central nervous system (CNS) lesion * Uveal and mucosal melanoma * History of leptomeningeal metastases * History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease * Any previous systemic chemotherapy treatment, extensive radiotherapy or investigational agent other than immunotherapy, or patients who have received more than one line of immunotherapy for locally advanced unresectable or metastatic melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at least 6 weeks prior to randomization * History of Gilbert's syndrome * Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor * Impaired cardiovascular function or clinically significant cardiovascular diseases * Uncontrolled arterial hypertension despite medical treatment * HIV positive or active Hepatitis B, and/or active Hepatitis C * Impairment of gastrointestinal function * Patients with neuromuscular disorders that are associated with elevated CK * Pregnant or nursing (lactating) women * Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Progression Free Survival (PFS) by BIRC in Combo 450 Group as Compared to Vemurafenib Group | From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months) | PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm\^2). |
| Part 1: PFS by BIRC in Combo 450 Group as Compared to LGX818 Group | From randomization until documented PD, initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group | PFS was defined as the time from the date of randomization to the date of the first documented PD or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: PFS by BIRC in Combo 300 Group as Compared to LGX818 Group | From randomization until documented PD, initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months) | PFS was defined as the time from the date of randomization to the date of the first documented PD or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2. |
| Part 1: Overall Survival (OS) | From randomization until censoring date/death, whichever occurred first (up to 117.8 months [M] of treatment exposure for LGX818 +MEK162; up to 111.4 months of treatment exposure for LGX818; up to 110.5 months of treatment exposure for Vemurafenib) | Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a death was not observed by the date of analysis cutoff, OS was censored at the date of last contact. |
| Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or an important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms; Grade 2: moderate; Grade 3: severe/medically significant; Grade 4: life-threatening consequence; Grade 5: death. AEs and SAEs of all grades combined were reported. |
| Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on NCI-CTCAE Grade, Version 4.03 | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | Laboratory parameters were graded using NCI-CTCAE v4.03 where, Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to \>=grade 3. Only categories with non-zero values for any reporting arm are reported. |
| Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | Notably abnormal vital signs were: low/high systolic blood pressure (SBP) (millimeter of mercury \[mmHg\]): \<= 90 mmHg with decrease from baseline of \>= 20 mmHg/\>= 160 mmHg with increase from baseline of \>=20 mmHg. Low/high diastolic blood pressure (DBP) (mmHg): \<= 50 mmHg with decrease from baseline of \>=15 mmHg/\>=100 mmHg with increase from baseline of \>=15 mmHg. Low/high Pulse rate: \<=50 beats per minute (bpm) with decrease from baseline of \>=15 bpm/\>= 120 bpm with increase from baseline of \>=15 bpm. Low/high Weight (kilogram): \>=20 percent (%) decrease from baseline/\>= 10% increase from baseline. Low/high body temperature degree Celsius (C): \<= 36 degree C/\>= 37.5 degree C. Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. |
| Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | Newly occurring notable ECG values were reported for QT (millisecond \[ms\]), QT corrected interval using Fridericia's correction (QTcF) (ms), QT corrected interval using Bazett's correction formula (QTcB) (ms) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Criteria for newly occurring notable ECG values (QT, QTcF, QTcB) were New \> 450, New \>480, New \>500, Increase from baseline \>30, Increase from baseline \>60; heart rate: New \<60, New \>100. |
| Part 1: Number of Participants With Worst Post-Baseline Left Ventricular Ejection Fraction (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | LVEF values were graded as Grade 0: non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline \>=10% and \< 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline \>=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. |
| Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the NCI-CTCAE v4.03 | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included severe cutaneous adverse reactions, cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma, and melanomas. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/ prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AESIs of grade 3 or 4 are reported in this outcome measure. |
| Part 1: Number of Participants With Ocular-related AESI Graded According to the NCI-CTCAE v4.03 | Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg) | AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/ prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Ocular related AESIs of grade 3 or 4 are reported in this outcome measure. |
| Part 2: Percentage of Participants With AEs and SAEs as Graded by NCI-CTCAE, Version 4.03 | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or an important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms; Grade 2: moderate; Grade 3: severe/medically significant; Grade 4: life-threatening consequence; Grade 5: death. AEs and SAEs of all grades combined were reported. |
| Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on NCI-CTCAE Grade, Version 4.03 | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | Laboratory parameters were graded using NCI-CTCAE v4.03 where, Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to \>=grade 3. Only categories with non-zero values for any reporting arm are reported. |
| Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | Notably abnormal vital signs were: low/high SBP (mmHg): \<= 90 mmHg with decrease from baseline of \>= 20 mmHg/\>= 160 mmHg with increase from baseline of \>=20 mmHg. Low/high DBP (mmHg): \<= 50 mmHg with decrease from baseline of \>=15 mmHg/\>=100 mmHg with increase from baseline of \>=15 mmHg. Low/high Pulse rate: \<=50 bpm with decrease from baseline of \>=15 bpm/\>= 120 bpm with increase from baseline of \>=15 bpm. Low/high Weight (kilogram): \>=20% decrease from baseline/\>= 10% increase from baseline. Low/high body temperature degree C: \<= 36 degree C/\>= 37.5 degree C. Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. |
| Part 2: Number of Participants With Newly Occurring Notable ECG Values | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Criteria for newly occurring notable ECG values (QT, QTcF, QTcB) were New \> 450, New \>480, New \>500, Increase from baseline \>30, Increase from baseline \>60; heart rate: New \<60, New \>100. |
| Part 2: Number of Participants With Worst Post-baseline LVEF Values by MUGA Scans or Transthoracic ECHO, by CTCAE Grade | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | LVEF values were graded as Grade 0: non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline \>=10% and \< 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline \>=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. |
| Part 2: Number of Participants With Dermatologic-related AESI Graded According to the NCI-CTCAE v4.03 | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included severe cutaneous adverse reactions, cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma and melanomas. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AESIs of grade 3 or 4 are reported are reported in this outcome measure. |
| Part 2: Number of Participants With Ocular-related AESI Graded According to the NCI-CTCAE v4.03 | Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg) | AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/ prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Ocular related AESIs of grade 3 or 4 are reported in this outcome measure. |
| Part (P) 2: Overall Survival (OS) | From randomization until censoring date/death, whichever occurred 1st (up to 106.3 M of treatment exposure for P2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for P2: LGX818 300 mg; up to 111.4 M of treatment exposure for P1+P2: LGX818 300 mg) | OS was defined as the time from the date of randomization to the date of death due to any cause. If a death was not observed by the date of analysis cutoff, OS was censored at the date of last contact. |
| Part 1 and Part 2: Objective Response Rate (ORR) | From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group) | ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure (OM). |
| Part 1 and Part 2: Time to Objective Response (TTR) | From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group) | TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit \[FPFV\] to last patient last visit \[LPLV\] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure. |
| Part 1 and Part 2: Disease Control Rate (DCR) | From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group) | DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure. |
| Part 1 and Part 2: Duration of Response (DOR) | From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group) | DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure. |
| Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group) | FACT-M:melanoma specific questionnaire to assess participant health-related quality of life(QoL).Melanoma specific 16 subscale :signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma.Other items :physical,functional and social/family well-being(7 items each),emotional well-being(6 items),surgery specific concerns related to melanoma(8 items,not included in this study).Each item range 0(not at all)to 4(very much),combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to172,higher scores:better QoL.Melanoma subscale score range from0(worst)to 64(best response),higher score:better QoL.Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.All collected data up to pre-specified collection period(i.e.,end of study)are reported for this OM. |
| Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group) | EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical,role,cognitive,emotional,social functioning), 3 multi-item symptom scales (fatigue,nausea/vomiting, and pain),global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea,sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score: better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure. |
| Part 1 and Part 2: Change From Baseline in the FACT-M Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug) | FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each), emotional well-being (6 items), surgery specific concerns related to melanoma (8 items, not included in this study). Each item ranged from 0 (not at all) to 4 (very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172, higher scores represented better quality of life. Melanoma subscale score ranged from 0 (worst response) to 64 (best response), higher score indicated better quality of life. |
| Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug) | EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. |
| Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug) | EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. |
| Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug) | EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/ QOL scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms. |
| Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug) | EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QOL scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms. |
| Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug) | EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QOL scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms. |
| Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31) | ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. |
| Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose | — |
| Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose | — |
| Part 1: Plasma Concentrations of MEK162 | Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose | — |
| Part 2: Plasma Concentrations of MEK162 | Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose | — |
| Part 1 and Part 2: Time to Definitive 1 Point Deterioration in ECOG PS | Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group) | ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure. |
Countries
Argentina, Australia, Brazil, Canada, Colombia, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
A total of 921 participants were enrolled in this study.
Pre-assignment details
Study closure by sponsor was used for the end of study reason since the per-protocol final OS analysis was performed and the study ended by sponsor per the EOS.Participants remaining on treatment at that time were allowed to continue treatment and roll over into the FLOTILLA continuation study (C4221026/NCT05203172)or move to another treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. | 192 |
| Part 1: LGX818 300 mg Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. | 194 |
| Part 1: Vemurafenib 960 mg BID Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. | 191 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. | 258 |
| Part 2: LGX818 300 mg Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. | 86 |
| Total | 921 |
Baseline characteristics
| Characteristic | Part 1: Vemurafenib 960 mg BID | Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 2: LGX818 300 mg | Total | Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: LGX818 300 mg |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 83 Participants | 26 Participants | 260 Participants | 60 Participants | 40 Participants |
| Age, Categorical Between 18 and 65 years | 140 Participants | 175 Participants | 60 Participants | 661 Participants | 132 Participants | 154 Participants |
| Sex: Female, Male Female | 80 Participants | 107 Participants | 42 Participants | 392 Participants | 77 Participants | 86 Participants |
| Sex: Female, Male Male | 111 Participants | 151 Participants | 44 Participants | 529 Participants | 115 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 171 / 257 | 136 / 192 | 125 / 192 | 60 / 84 | 145 / 186 |
| other Total, other adverse events | 252 / 257 | 189 / 192 | 190 / 192 | 82 / 84 | 185 / 186 |
| serious Total, serious adverse events | 98 / 257 | 84 / 192 | 71 / 192 | 31 / 84 | 78 / 186 |
Outcome results
Primary
Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2.
Time frame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group | 14.9 months |
| Part 1: Vemurafenib 960 mg BID | Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group | 9.6 months |
Primary
Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm\^2).
Time frame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group | 14.9 months |
| Part 1: Vemurafenib 960 mg BID | Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group | 7.3 months |
Secondary
Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 3.52 units on a scale | Standard Deviation 23.715 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | 3.92 units on a scale | Standard Deviation 11.456 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 4.17 units on a scale | Standard Deviation 19.811 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 3.23 units on a scale | Standard Deviation 20.588 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 5.42 units on a scale | Standard Deviation 20.027 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -1.74 units on a scale | Standard Deviation 21.42 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 74.68 units on a scale | Standard Deviation 21.233 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 4.25 units on a scale | Standard Deviation 19.552 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 5.37 units on a scale | Standard Deviation 19.243 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 5.33 units on a scale | Standard Deviation 20.584 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 4.47 units on a scale | Standard Deviation 24.341 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 4.81 units on a scale | Standard Deviation 22.102 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 41.67 units on a scale | Standard Deviation 11.785 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 7.35 units on a scale | Standard Deviation 21.813 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 2.30 units on a scale | Standard Deviation 20.755 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 3.78 units on a scale | Standard Deviation 19.694 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 0.12 units on a scale | Standard Deviation 22.205 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -0.32 units on a scale | Standard Deviation 24.093 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -0.34 units on a scale | Standard Deviation 22.138 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 74.46 units on a scale | Standard Deviation 22.367 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | 2.94 units on a scale | Standard Deviation 22.556 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 1.54 units on a scale | Standard Deviation 22.418 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -3.57 units on a scale | Standard Deviation 25.394 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -1.16 units on a scale | Standard Deviation 23.751 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 1.00 units on a scale | Standard Deviation 24.493 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 0.34 units on a scale | Standard Deviation 23.104 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 3.64 units on a scale | Standard Deviation 21.502 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 2.15 units on a scale | Standard Deviation 19.735 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 2.71 units on a scale | Standard Deviation 20.875 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 72.31 units on a scale | Standard Deviation 24.695 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 1.88 units on a scale | Standard Deviation 20.61 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 2.03 units on a scale | Standard Deviation 20.662 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.17 units on a scale | Standard Deviation 24.283 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 4.53 units on a scale | Standard Deviation 18.148 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -2.25 units on a scale | Standard Deviation 22.192 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -5.46 units on a scale | Standard Deviation 26.19 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -1.39 units on a scale | Standard Deviation 15.862 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 0.38 units on a scale | Standard Deviation 16.158 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -3.13 units on a scale | Standard Deviation 16.908 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -0.69 units on a scale | Standard Deviation 23.693 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -1.19 units on a scale | Standard Deviation 34.503 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 12.50 units on a scale | Standard Deviation 28.464 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 9.37 units on a scale | Standard Deviation 21.088 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 13.13 units on a scale | Standard Deviation 15.619 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 73.04 units on a scale | Standard Deviation 24.45 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 8.33 units on a scale | Standard Deviation 22.997 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 10.56 units on a scale | Standard Deviation 20.85 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 6.15 units on a scale | Standard Deviation 21.401 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 7.29 units on a scale | Standard Deviation 20.011 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 8.66 units on a scale | Standard Deviation 21.894 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 10.59 units on a scale | Standard Deviation 19.609 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 10.33 units on a scale | Standard Deviation 20.415 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 9.22 units on a scale | Standard Deviation 21.94 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -4.17 units on a scale | Standard Deviation 14.434 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.60 units on a scale | Standard Deviation 16.296 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -2.12 units on a scale | Standard Deviation 13.232 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -3.62 units on a scale | Standard Deviation 19.441 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 74.20 units on a scale | Standard Deviation 21.488 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 1.79 units on a scale | Standard Deviation 15.736 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 2.78 units on a scale | Standard Deviation 16.667 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 2.96 units on a scale | Standard Deviation 20.473 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 16.67 units on a scale | — |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 1.79 units on a scale | Standard Deviation 19.958 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -2.69 units on a scale | Standard Deviation 17.793 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 5.56 units on a scale | Standard Deviation 4.811 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -6.41 units on a scale | Standard Deviation 17.998 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 0.32 units on a scale | Standard Deviation 21.465 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 0.83 units on a scale | Standard Deviation 19.675 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 3.26 units on a scale | Standard Deviation 20.373 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | 2.94 units on a scale | Standard Deviation 22.556 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -0.91 units on a scale | Standard Deviation 22.033 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 74.38 units on a scale | Standard Deviation 22.054 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -0.32 units on a scale | Standard Deviation 24.093 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.74 units on a scale | Standard Deviation 20.915 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 1.30 units on a scale | Standard Deviation 19.317 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 1.27 units on a scale | Standard Deviation 23.357 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.83 units on a scale | Standard Deviation 21.318 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 1.98 units on a scale | Standard Deviation 21.796 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 1.26 units on a scale | Standard Deviation 18.674 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.76 units on a scale | Standard Deviation 23.626 |
Secondary
Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | 0.07 units on a scale | Standard Deviation 0.135 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 0.03 units on a scale | Standard Deviation 0.237 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | 0.04 units on a scale | Standard Deviation 0.139 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 0.04 units on a scale | Standard Deviation 0.196 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 0.07 units on a scale | Standard Deviation 0.193 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 0.05 units on a scale | Standard Deviation 0.208 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 0.04 units on a scale | Standard Deviation 0.197 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 0.05 units on a scale | Standard Deviation 0.194 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 0.03 units on a scale | Standard Deviation 0.081 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 0.74 units on a scale | Standard Deviation 0.21 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 0.05 units on a scale | Standard Deviation 0.201 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 0.03 units on a scale | Standard Deviation 0.239 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 0.07 units on a scale | Standard Deviation 0.132 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 0.05 units on a scale | Standard Deviation 0.225 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.09 units on a scale | Standard Deviation 0.347 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -0.11 units on a scale | Standard Deviation 0.147 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -0.11 units on a scale | Standard Deviation 0.207 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.18 units on a scale | Standard Deviation 0.206 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -0.15 units on a scale | Standard Deviation 0.22 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.17 units on a scale | Standard Deviation 0.206 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.15 units on a scale | Standard Deviation 0.197 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -0.18 units on a scale | Standard Deviation 0.203 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -0.10 units on a scale | Standard Deviation 0.199 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -0.14 units on a scale | Standard Deviation 0.165 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 0.76 units on a scale | Standard Deviation 0.181 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.18 units on a scale | Standard Deviation 0.235 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.14 units on a scale | Standard Deviation 0.198 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -0.13 units on a scale | Standard Deviation 0.189 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.02 units on a scale | Standard Deviation 0.263 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 0.73 units on a scale | Standard Deviation 0.222 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -0.05 units on a scale | Standard Deviation 0.171 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -0.04 units on a scale | Standard Deviation 0.196 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.04 units on a scale | Standard Deviation 0.159 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.02 units on a scale | Standard Deviation 0.214 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -0.03 units on a scale | Standard Deviation 0.215 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.01 units on a scale | Standard Deviation 0.238 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.04 units on a scale | Standard Deviation 0.237 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.14 units on a scale | Standard Deviation 0.103 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -0.07 units on a scale | Standard Deviation 0.28 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 0.00 units on a scale | Standard Deviation 0.196 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -0.17 units on a scale | Standard Deviation 0.221 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -0.02 units on a scale | Standard Deviation 0.173 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 0.06 units on a scale | Standard Deviation 0.195 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 0.07 units on a scale | Standard Deviation 0.192 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 0.05 units on a scale | Standard Deviation 0.254 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 0.05 units on a scale | Standard Deviation 0.259 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 0.06 units on a scale | Standard Deviation 0.188 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 0.05 units on a scale | Standard Deviation 0.231 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 0.12 units on a scale | Standard Deviation 0.174 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.27 units on a scale | Standard Deviation 0.481 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 0.75 units on a scale | Standard Deviation 0.219 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 0.06 units on a scale | Standard Deviation 0.204 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 0.07 units on a scale | Standard Deviation 0.218 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 0.06 units on a scale | Standard Deviation 0.237 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 0.73 units on a scale | Standard Deviation 0.244 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.20 units on a scale | Standard Deviation 0.216 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.06 units on a scale | Standard Deviation 0.061 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.16 units on a scale | Standard Deviation 0.23 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -0.16 units on a scale | Standard Deviation 0.22 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -0.06 units on a scale | Standard Deviation 0.231 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -0.20 units on a scale | Standard Deviation 0.332 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -0.26 units on a scale | Standard Deviation 0.262 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.11 units on a scale | Standard Deviation 0.328 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.11 units on a scale | Standard Deviation 0.202 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.11 units on a scale | — |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -0.06 units on a scale | Standard Deviation 0.246 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.14 units on a scale | Standard Deviation 0.196 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -0.14 units on a scale | Standard Deviation 0.199 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.17 units on a scale | Standard Deviation 0.249 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.08 units on a scale | Standard Deviation 0.249 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -0.15 units on a scale | Standard Deviation 0.203 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.14 units on a scale | Standard Deviation 0.199 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 0.75 units on a scale | Standard Deviation 0.203 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -0.20 units on a scale | Standard Deviation 0.218 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.18 units on a scale | Standard Deviation 0.208 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -0.09 units on a scale | Standard Deviation 0.214 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.17 units on a scale | Standard Deviation 0.213 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -0.13 units on a scale | Standard Deviation 0.227 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -0.11 units on a scale | Standard Deviation 0.147 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -0.11 units on a scale | Standard Deviation 0.207 |
Secondary
Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms.
Time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 0.42 units on a scale | Standard Deviation 22.642 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | 1.96 units on a scale | Standard Deviation 13.349 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 0.74 units on a scale | Standard Deviation 16.838 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 3.56 units on a scale | Standard Deviation 22.463 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 1.53 units on a scale | Standard Deviation 23.22 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -1.39 units on a scale | Standard Deviation 13.157 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 66.72 units on a scale | Standard Deviation 21.585 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.51 units on a scale | Standard Deviation 17.547 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 1.55 units on a scale | Standard Deviation 23.441 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 0.41 units on a scale | Standard Deviation 21.807 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.55 units on a scale | Standard Deviation 25.5 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 0.81 units on a scale | Standard Deviation 21.67 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 0.00 units on a scale | Standard Deviation 11.785 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 5.02 units on a scale | Standard Deviation 19.108 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -9.91 units on a scale | Standard Deviation 23.49 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -8.59 units on a scale | Standard Deviation 22.516 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -11.27 units on a scale | Standard Deviation 20.611 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -7.05 units on a scale | Standard Deviation 18.057 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -7.64 units on a scale | Standard Deviation 21.564 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 66.07 units on a scale | Standard Deviation 21.89 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -5.64 units on a scale | Standard Deviation 19.754 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -9.24 units on a scale | Standard Deviation 21.611 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 4.76 units on a scale | Standard Deviation 28.81 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -11.05 units on a scale | Standard Deviation 21.725 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -9.33 units on a scale | Standard Deviation 19.169 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -9.21 units on a scale | Standard Deviation 23.528 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -8.03 units on a scale | Standard Deviation 17.784 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -12.03 units on a scale | Standard Deviation 19.771 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -3.04 units on a scale | Standard Deviation 28.197 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 64.74 units on a scale | Standard Deviation 23.611 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -3.46 units on a scale | Standard Deviation 25.235 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -4.05 units on a scale | Standard Deviation 23.7 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -6.94 units on a scale | Standard Deviation 21.512 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -3.80 units on a scale | Standard Deviation 22.202 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -2.93 units on a scale | Standard Deviation 20.621 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -10.34 units on a scale | Standard Deviation 29.852 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -6.94 units on a scale | Standard Deviation 20.214 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -1.89 units on a scale | Standard Deviation 20.401 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -8.85 units on a scale | Standard Deviation 11.968 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -3.47 units on a scale | Standard Deviation 18.278 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -2.38 units on a scale | Standard Deviation 19.67 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -4.17 units on a scale | Standard Deviation 10.758 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 5.01 units on a scale | Standard Deviation 24 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 3.03 units on a scale | Standard Deviation 19.816 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 65.95 units on a scale | Standard Deviation 23.028 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 1.23 units on a scale | Standard Deviation 18.155 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 4.76 units on a scale | Standard Deviation 21.212 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 5.61 units on a scale | Standard Deviation 19.396 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 4.47 units on a scale | Standard Deviation 23.031 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 5.89 units on a scale | Standard Deviation 23.642 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 6.11 units on a scale | Standard Deviation 21.695 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 5.86 units on a scale | Standard Deviation 21.806 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 4.94 units on a scale | Standard Deviation 20.258 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -6.25 units on a scale | Standard Deviation 18.478 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -8.73 units on a scale | Standard Deviation 18.945 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -12.75 units on a scale | Standard Deviation 21.27 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -7.08 units on a scale | Standard Deviation 20.955 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 67.39 units on a scale | Standard Deviation 22.095 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -7.14 units on a scale | Standard Deviation 20.111 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.93 units on a scale | Standard Deviation 12.805 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -4.72 units on a scale | Standard Deviation 22.776 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 0.00 units on a scale | — |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -4.95 units on a scale | Standard Deviation 20.378 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -7.53 units on a scale | Standard Deviation 19.288 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 4.17 units on a scale | Standard Deviation 29.463 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -9.29 units on a scale | Standard Deviation 24.645 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -6.81 units on a scale | Standard Deviation 21.199 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -8.80 units on a scale | Standard Deviation 23.013 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -7.85 units on a scale | Standard Deviation 18.127 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -5.64 units on a scale | Standard Deviation 19.754 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -8.53 units on a scale | Standard Deviation 22.701 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 66.48 units on a scale | Standard Deviation 21.92 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -7.05 units on a scale | Standard Deviation 18.057 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -10.13 units on a scale | Standard Deviation 20.197 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -10.56 units on a scale | Standard Deviation 22.897 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -8.05 units on a scale | Standard Deviation 18.503 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 4.63 units on a scale | Standard Deviation 27.039 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -7.87 units on a scale | Standard Deviation 22.011 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -10.96 units on a scale | Standard Deviation 19.496 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -10.80 units on a scale | Standard Deviation 21.535 |
Secondary
Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -1.25 units on a scale | Standard Deviation 19.705 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -5.49 units on a scale | Standard Deviation 14.575 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.95 units on a scale | Standard Deviation 13.15 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 0.20 units on a scale | Standard Deviation 18.033 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -1.93 units on a scale | Standard Deviation 18.071 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -5.00 units on a scale | Standard Deviation 13.656 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 82.10 units on a scale | Standard Deviation 19.593 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -1.22 units on a scale | Standard Deviation 16.14 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 0.15 units on a scale | Standard Deviation 18.388 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -0.03 units on a scale | Standard Deviation 17.862 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -0.45 units on a scale | Standard Deviation 20.511 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.85 units on a scale | Standard Deviation 18.767 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 33.33 units on a scale | Standard Deviation 47.14 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 0.29 units on a scale | Standard Deviation 17.356 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -20.26 units on a scale | Standard Deviation 21.03 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -20.00 units on a scale | Standard Deviation 20.874 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -22.65 units on a scale | Standard Deviation 20.867 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -15.93 units on a scale | Standard Deviation 17.092 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -13.79 units on a scale | Standard Deviation 20.396 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 83.18 units on a scale | Standard Deviation 20.266 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -14.46 units on a scale | Standard Deviation 18.298 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -17.14 units on a scale | Standard Deviation 22.276 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -0.95 units on a scale | Standard Deviation 22.91 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -16.86 units on a scale | Standard Deviation 19.694 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -20.07 units on a scale | Standard Deviation 21.417 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -16.26 units on a scale | Standard Deviation 21.719 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -18.88 units on a scale | Standard Deviation 20.072 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -19.43 units on a scale | Standard Deviation 20.755 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -6.98 units on a scale | Standard Deviation 19.605 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 80.71 units on a scale | Standard Deviation 22.182 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -2.90 units on a scale | Standard Deviation 20.319 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -7.45 units on a scale | Standard Deviation 17.792 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -6.82 units on a scale | Standard Deviation 21.881 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -4.11 units on a scale | Standard Deviation 18.68 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -6.30 units on a scale | Standard Deviation 22.534 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -6.22 units on a scale | Standard Deviation 21.58 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -3.27 units on a scale | Standard Deviation 19.817 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -1.90 units on a scale | Standard Deviation 20.237 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -4.90 units on a scale | Standard Deviation 19.355 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -2.22 units on a scale | Standard Deviation 19.557 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -4.76 units on a scale | Standard Deviation 23.637 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -15.00 units on a scale | Standard Deviation 19.149 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 1.22 units on a scale | Standard Deviation 17.469 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -8.48 units on a scale | Standard Deviation 23.303 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 80.67 units on a scale | Standard Deviation 21.889 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -5.71 units on a scale | Standard Deviation 16.301 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 0.50 units on a scale | Standard Deviation 17.734 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 2.73 units on a scale | Standard Deviation 17.748 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 2.94 units on a scale | Standard Deviation 16.831 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 0.47 units on a scale | Standard Deviation 18.29 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -0.40 units on a scale | Standard Deviation 22.466 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -0.88 units on a scale | Standard Deviation 16.432 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 3.03 units on a scale | Standard Deviation 16.525 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -5.00 units on a scale | Standard Deviation 10 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -15.83 units on a scale | Standard Deviation 16.269 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -24.31 units on a scale | Standard Deviation 22.845 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -17.01 units on a scale | Standard Deviation 20.2 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 81.45 units on a scale | Standard Deviation 21.89 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -19.05 units on a scale | Standard Deviation 23.367 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -14.07 units on a scale | Standard Deviation 14.699 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -12.63 units on a scale | Standard Deviation 21.57 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -13.33 units on a scale | — |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -13.63 units on a scale | Standard Deviation 22.428 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -13.49 units on a scale | Standard Deviation 13.665 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -4.44 units on a scale | Standard Deviation 3.849 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -13.85 units on a scale | Standard Deviation 17.781 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -13.74 units on a scale | Standard Deviation 20.994 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -18.22 units on a scale | Standard Deviation 20.127 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -18.91 units on a scale | Standard Deviation 20.599 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -14.46 units on a scale | Standard Deviation 18.298 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -16.49 units on a scale | Standard Deviation 21.194 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 82.63 units on a scale | Standard Deviation 20.766 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -15.93 units on a scale | Standard Deviation 17.092 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -19.87 units on a scale | Standard Deviation 19.369 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -21.18 units on a scale | Standard Deviation 21.364 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -19.14 units on a scale | Standard Deviation 20.527 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -2.00 units on a scale | Standard Deviation 18.869 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -15.74 units on a scale | Standard Deviation 22.104 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -18.27 units on a scale | Standard Deviation 19.429 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -16.78 units on a scale | Standard Deviation 19.471 |
Secondary
Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -4.27 units on a scale | Standard Deviation 28.228 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -5.21 units on a scale | Standard Deviation 23.348 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -1.52 units on a scale | Standard Deviation 32.103 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -0.66 units on a scale | Standard Deviation 27.854 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 2.82 units on a scale | Standard Deviation 28.807 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -12.32 units on a scale | Standard Deviation 28.077 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 80.69 units on a scale | Standard Deviation 24.696 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -1.04 units on a scale | Standard Deviation 30.248 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 3.26 units on a scale | Standard Deviation 27.559 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 1.11 units on a scale | Standard Deviation 27.251 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 1.57 units on a scale | Standard Deviation 31.834 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -2.72 units on a scale | Standard Deviation 29.16 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 25.00 units on a scale | Standard Deviation 35.355 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 3.73 units on a scale | Standard Deviation 25.921 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -10.63 units on a scale | Standard Deviation 27.695 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -11.38 units on a scale | Standard Deviation 28.053 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -12.62 units on a scale | Standard Deviation 27.428 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -7.05 units on a scale | Standard Deviation 24.117 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -10.86 units on a scale | Standard Deviation 28.967 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 80.91 units on a scale | Standard Deviation 23.841 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -6.37 units on a scale | Standard Deviation 20.521 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -11.92 units on a scale | Standard Deviation 32.145 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -19.05 units on a scale | Standard Deviation 26.227 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -14.73 units on a scale | Standard Deviation 30.257 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -12.33 units on a scale | Standard Deviation 30.826 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -9.80 units on a scale | Standard Deviation 28.979 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -11.42 units on a scale | Standard Deviation 25.865 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -15.71 units on a scale | Standard Deviation 26.579 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -2.75 units on a scale | Standard Deviation 31.586 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 78.54 units on a scale | Standard Deviation 26.854 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -4.90 units on a scale | Standard Deviation 30.097 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -7.21 units on a scale | Standard Deviation 27.026 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -1.99 units on a scale | Standard Deviation 30.084 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.36 units on a scale | Standard Deviation 28.865 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.45 units on a scale | Standard Deviation 27.635 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -6.32 units on a scale | Standard Deviation 34.622 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 1.39 units on a scale | Standard Deviation 25.02 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 3.79 units on a scale | Standard Deviation 26.192 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -3.13 units on a scale | Standard Deviation 22.948 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | 1.39 units on a scale | Standard Deviation 15.006 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | 4.76 units on a scale | Standard Deviation 20.893 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -8.33 units on a scale | Standard Deviation 9.623 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 3.05 units on a scale | Standard Deviation 22.185 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 4.55 units on a scale | Standard Deviation 18.395 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 81.37 units on a scale | Standard Deviation 25.262 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 1.23 units on a scale | Standard Deviation 22.133 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 1.95 units on a scale | Standard Deviation 23.032 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 3.37 units on a scale | Standard Deviation 20.604 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 4.05 units on a scale | Standard Deviation 22.461 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 1.75 units on a scale | Standard Deviation 24.585 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 2.86 units on a scale | Standard Deviation 22.34 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 1.59 units on a scale | Standard Deviation 22.543 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 3.66 units on a scale | Standard Deviation 21.002 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -16.67 units on a scale | Standard Deviation 30.429 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -9.52 units on a scale | Standard Deviation 14.79 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -15.69 units on a scale | Standard Deviation 16.106 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -13.89 units on a scale | Standard Deviation 27.992 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 78.31 units on a scale | Standard Deviation 28.6 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -7.14 units on a scale | Standard Deviation 28.28 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -12.96 units on a scale | Standard Deviation 34.134 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -5.11 units on a scale | Standard Deviation 28.244 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -33.33 units on a scale | — |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -10.00 units on a scale | Standard Deviation 26.829 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -12.37 units on a scale | Standard Deviation 23.161 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 0.00 units on a scale | Standard Deviation 33.333 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -5.77 units on a scale | Standard Deviation 18.822 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -10.59 units on a scale | Standard Deviation 28.262 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -9.74 units on a scale | Standard Deviation 25.723 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -10.54 units on a scale | Standard Deviation 26.219 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -6.37 units on a scale | Standard Deviation 20.521 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -11.11 units on a scale | Standard Deviation 28.646 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 80.09 units on a scale | Standard Deviation 25.418 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -7.05 units on a scale | Standard Deviation 24.117 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -12.54 units on a scale | Standard Deviation 26.077 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -11.78 units on a scale | Standard Deviation 25.524 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -12.43 units on a scale | Standard Deviation 31.041 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -13.33 units on a scale | Standard Deviation 28.109 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -9.80 units on a scale | Standard Deviation 31.073 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -13.70 units on a scale | Standard Deviation 23.52 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -15.15 units on a scale | Standard Deviation 30.034 |
Secondary
Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life.
Time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.33 units on a scale | Standard Deviation 8.855 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -1.83 units on a scale | Standard Deviation 6.205 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -0.69 units on a scale | Standard Deviation 6.947 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 0.92 units on a scale | Standard Deviation 9.539 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 1.35 units on a scale | Standard Deviation 9.595 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -1.67 units on a scale | Standard Deviation 7.003 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 52.39 units on a scale | Standard Deviation 9.053 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -0.59 units on a scale | Standard Deviation 7.257 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -0.01 units on a scale | Standard Deviation 9.157 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 0.27 units on a scale | Standard Deviation 7.775 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 0.52 units on a scale | Standard Deviation 9.096 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 0.18 units on a scale | Standard Deviation 7.768 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 18.50 units on a scale | Standard Deviation 23.335 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 0.40 units on a scale | Standard Deviation 7.943 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -2.48 units on a scale | Standard Deviation 6.829 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -2.71 units on a scale | Standard Deviation 7.187 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -3.67 units on a scale | Standard Deviation 6.418 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -1.00 units on a scale | Standard Deviation 6.88 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -3.58 units on a scale | Standard Deviation 8.133 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 52.76 units on a scale | Standard Deviation 8.206 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -1.38 units on a scale | Standard Deviation 6.818 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -3.77 units on a scale | Standard Deviation 7.576 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -5.18 units on a scale | Standard Deviation 11.458 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -2.59 units on a scale | Standard Deviation 6.528 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -2.80 units on a scale | Standard Deviation 6.172 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -3.05 units on a scale | Standard Deviation 6.633 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -1.66 units on a scale | Standard Deviation 6.681 |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -2.69 units on a scale | Standard Deviation 6.513 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -2.19 units on a scale | Standard Deviation 8.651 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 52.01 units on a scale | Standard Deviation 8.65 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -1.55 units on a scale | Standard Deviation 9.023 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -1.90 units on a scale | Standard Deviation 7.572 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -1.90 units on a scale | Standard Deviation 7.491 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -0.51 units on a scale | Standard Deviation 7.436 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -0.97 units on a scale | Standard Deviation 8.818 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -1.72 units on a scale | Standard Deviation 9.906 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 0.70 units on a scale | Standard Deviation 6.071 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 0.23 units on a scale | Standard Deviation 9.094 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -3.33 units on a scale | Standard Deviation 6.399 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -0.17 units on a scale | Standard Deviation 4.687 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -0.14 units on a scale | Standard Deviation 5.305 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -2.31 units on a scale | Standard Deviation 4.715 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | 2.64 units on a scale | Standard Deviation 7.766 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | 2.58 units on a scale | Standard Deviation 8.218 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 52.08 units on a scale | Standard Deviation 8.493 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 1.23 units on a scale | Standard Deviation 10.618 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | 2.54 units on a scale | Standard Deviation 7.796 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | 2.58 units on a scale | Standard Deviation 7.244 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | 2.79 units on a scale | Standard Deviation 7.296 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | 1.97 units on a scale | Standard Deviation 8.127 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | 2.08 units on a scale | Standard Deviation 9.196 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | 2.45 units on a scale | Standard Deviation 9.012 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | 3.23 units on a scale | Standard Deviation 7.72 |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | 6.58 units on a scale | Standard Deviation 7.197 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -1.83 units on a scale | Standard Deviation 7.323 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -4.14 units on a scale | Standard Deviation 5.662 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -3.14 units on a scale | Standard Deviation 9.559 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 51.13 units on a scale | Standard Deviation 9.567 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -2.64 units on a scale | Standard Deviation 9.724 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | 0.00 units on a scale | Standard Deviation 11.467 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -0.60 units on a scale | Standard Deviation 7.948 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -2.00 units on a scale | — |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -2.16 units on a scale | Standard Deviation 9.7 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -2.41 units on a scale | Standard Deviation 7.653 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -1.61 units on a scale | Standard Deviation 9.115 |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -3.31 units on a scale | Standard Deviation 7.902 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 3 Day 1 | -3.14 units on a scale | Standard Deviation 8.654 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 13 Day 1 | -2.88 units on a scale | Standard Deviation 7.359 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 17 Day 1 | -1.88 units on a scale | Standard Deviation 7.375 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 23 Day 1 | -1.38 units on a scale | Standard Deviation 6.818 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 7 Day 1 | -3.08 units on a scale | Standard Deviation 7.67 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Baseline | 52.24 units on a scale | Standard Deviation 8.679 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 25 Day 1 | -1.00 units on a scale | Standard Deviation 6.88 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 11 Day 1 | -3.29 units on a scale | Standard Deviation 6.8 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 15 Day 1 | -2.88 units on a scale | Standard Deviation 6.566 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 19 Day 1 | -2.38 units on a scale | Standard Deviation 7.15 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at End of treatment visit | -3.81 units on a scale | Standard Deviation 10.37 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 5 Day 1 | -2.78 units on a scale | Standard Deviation 7.814 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 9 Day 1 | -2.39 units on a scale | Standard Deviation 6.782 |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit | Change at Cycle 21 Day 1 | -2.58 units on a scale | Standard Deviation 6.445 |
Secondary
Part 1 and Part 2: Disease Control Rate (DCR)
DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review.
Time frame: From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Population: FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Disease Control Rate (DCR) | 92.2 percentage of participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Disease Control Rate (DCR) | 84.0 percentage of participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Disease Control Rate (DCR) | 81.7 percentage of participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Disease Control Rate (DCR) | 90.7 percentage of participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Disease Control Rate (DCR) | 79.1 percentage of participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Disease Control Rate (DCR) | 82.5 percentage of participants |
Secondary
Part 1 and Part 2: Duration of Response (DOR)
DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response.
Time frame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Population: Analysis population included all the participants who achieved at least once confirmed CR or PR. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Duration of Response (DOR) | 16.6 months |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Duration of Response (DOR) | 15.2 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Duration of Response (DOR) | 12.3 months |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Duration of Response (DOR) | 12.7 months |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Duration of Response (DOR) | 7.5 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Duration of Response (DOR) | 12.9 months |
Secondary
Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead.
Time frame: Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, Number analyzed signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm. Data is reported only for categories with non-zero values.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 0 | 60 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 0 | 24 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 3 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 2 | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 1 | 44 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 1 | 56 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 2 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 0 | 65 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 1 | 36 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 1 | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 0 | 124 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 0 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 0 | 102 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 2 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 1 | 45 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 2 | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 3 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 2 | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 2 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 1 | 16 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 3 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 1 | 33 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 1 | 8 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 0 | 36 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 1 | 14 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 0 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 1 | 30 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 1 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 0 | 29 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 3 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 0 | 112 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 0 | 111 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 1 | 53 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 1 | 10 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 2 | 9 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 1 | 46 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 1 | 22 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 0 | 131 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 0 | 72 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 0 | 77 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 0 | 88 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 0 | 128 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 1 | 20 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 2 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 0 | 5 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 0 | 54 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 1 | 50 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 1 | 24 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 1 | 32 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 0 | 142 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 0 | 94 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 1 | 25 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 0 | 74 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 0 | 136 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 1 | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 1 | 9 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 5 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 4 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 0 | 21 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 0 | 128 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 4 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 0 | 64 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 2 | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 1 | 23 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 1 | 42 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 1 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 0 | 5 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 1 | 6 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 3 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 2 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 0 | 84 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 0 | 53 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 1 | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 1 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 2 | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 1 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 0 | 14 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 0 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 1 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 1 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 0 | 17 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 1 | 8 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 2 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 1 | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 1 | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 0 | 7 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 0 | 23 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 1 | 8 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 0 | 21 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 0 | 36 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 1 | 31 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 1 | 6 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 2 | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 1 | 23 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 0 | 47 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 2 | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 0 | 41 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 1 | 27 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 2 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 4 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 0 | 20 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 0 | 41 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 1 | 30 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 0 | 93 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 1 | 66 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 1 | 10 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 2 | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 0 | 98 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 3 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 0 | 23 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 0 | 85 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 0 | 139 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 1 | 12 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 1 | 69 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 1 | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 2 | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 0 | 26 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 4 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 1 | 79 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 0 | 68 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 3 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 1 | 65 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 1 | 16 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 2 | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 0 | 13 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 0 | 27 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 4 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 0 | 68 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 2 | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 1 | 60 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 1 | 19 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 0 | 9 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 0 | 29 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 0 | 55 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 1 | 49 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 2 | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 2 | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 3 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 3 | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 0 | 50 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 1 | 19 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 1 | 47 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 0 | 31 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 1 | 6 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 1 | 20 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 5 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 0 | 52 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 0 | 38 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 1 | 35 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 1 | 53 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 0 | 18 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 2 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 0 | 44 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 1 | 40 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 0 | 90 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 1 | 24 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 0 | 41 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 0 | 44 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 1 | 31 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 1 | 27 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 2 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 3 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 1 | 81 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 0 | 39 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 2 | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 0 | 10 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 1 | 52 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 1 | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 0 | 82 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 1 | 64 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 0 | 113 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 1 | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 0 | 32 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 3 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 1 | 19 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 5 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 0 | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 1 | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 0 | 25 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 0 | 43 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 0 | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 0 | 24 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 1 | 52 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 1 | 26 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 1 | 16 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 2 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 1 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 1 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 0 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 1 | 11 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 0 | 98 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 1 | 18 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 0 | 135 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 0 | 27 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 0 | 22 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 0 | 39 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 1 | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 1 | 11 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 1 | 35 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 0 | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 0 | 74 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 2 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 1 | 10 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 1 | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 0 | 15 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 0 | 21 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 0 | 58 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 0 | 11 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 0 | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 1 | 33 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 1 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 1 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 1 | 18 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 0 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 2 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 1 | 46 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 0 | 107 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 0 | 18 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 1 | 64 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 1 | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 0 | 78 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 0 | 55 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 4 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 1 | 30 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 0 | 19 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 1 | 51 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 0 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 0 | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 1 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 1 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 0 | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 1 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 0 | 22 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 0 | 189 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 1 | 68 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 0 | 193 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 1 | 62 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 0 | 197 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 1 | 55 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 0 | 189 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 1 | 56 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 2 | 4 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 0 | 181 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 1 | 55 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 0 | 168 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 1 | 58 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 2 | 3 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 4 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 0 | 158 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 1 | 58 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 0 | 140 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 1 | 58 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 0 | 135 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 1 | 52 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 4 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 5 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 0 | 121 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 1 | 46 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 2 | 3 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 0 | 116 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 1 | 42 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 0 | 113 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 1 | 38 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 4 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 0 | 102 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 1 | 39 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 4 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 0 | 100 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 1 | 33 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 0 | 82 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 1 | 27 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 4 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 0 | 64 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 1 | 23 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 0 | 52 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 1 | 15 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 0 | 34 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 1 | 11 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 1 | 7 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 0 | 15 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 1 | 5 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 0 | 11 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 1 | 2 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 0 | 4 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 1 | 2 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 0 | 14 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 1 | 24 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 0 | 9 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 1 | 18 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 1 | 6 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 0 | 11 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 0 | 40 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 2 | 3 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 0 | 5 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 1 | 16 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 1 | 5 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 0 | 17 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 1 | 18 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 0 | 18 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 0 | 2 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 5 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 1 | 6 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 1 | 20 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 0 | 3 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 0 | 22 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 1 | 3 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 2 | 3 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 0 | 60 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 1 | 21 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 0 | 22 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 0 | 2 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 1 | 27 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 2 | 4 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 1 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 0 | 27 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 3 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 1 | 32 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 2 | 3 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 1 | 25 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 0 | 29 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 1 | 31 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 0 | 33 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 0 | 44 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 2 | 3 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 1 | 30 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 2 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 0 | 35 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 1 | 7 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 0 | 13 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 3 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 1 | 10 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 0 | 15 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 0 | 11 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 4 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 2 | 2 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 1 | 32 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 1 | 7 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 1 | 15 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 2 | 1 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 1 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 0 | 0 Participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 1 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 0 | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 1 | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 0 | 21 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 1 | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 25 Day 1: ECOG score 0 | 23 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 1 | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 31 Day 1: ECOG score 1 | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 1 | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 2 | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 4 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 1 | 37 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 1 | 111 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 1 | 10 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 0 | 48 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 1 | 49 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 0 | 128 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 1 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 2 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 1 | 33 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 12 Day 1: ECOG score 0 | 55 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 27 Day 1: ECOG score 0 | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 0 | 27 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 17 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 26 Day 1: ECOG score 2 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 2 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 1 | 90 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 0 | 55 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 0 | 41 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 1 | 56 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 30 Day 1: ECOG score 0 | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 11 Day 1: ECOG score 0 | 61 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 2 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 1 | 16 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 1 | 29 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 6 Day 1: ECOG score 0 | 97 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 0 | 54 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 0 | 199 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 2 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 1 | 53 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 0 | 62 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 18 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 1 | 37 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 10 Day 1: ECOG score 0 | 70 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 5 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 0 | 130 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 0 | 40 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 0 | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 4 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 0 | 18 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 22 Day 1: ECOG score 4 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 1 | 26 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 2 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 3 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 19 Day 1: ECOG score 2 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 1 | 100 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 1 | 67 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 0 | 142 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 29 Day 1: ECOG score 1 | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 0 | 26 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 0 | 34 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 9 Day 1: ECOG score 0 | 72 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 3 Day 1: ECOG score 1 | 113 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 2 Day 1: ECOG score 2 | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 5 Day 1: ECOG score 0 | 118 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 1 | 22 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 2 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 1 | 30 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 23 Day 1: ECOG score 1 | 12 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 1 | 70 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 3 | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 8 Day 1: ECOG score 0 | 77 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 14 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 2 | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 20 Day 1: ECOG score 3 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline: ECOG score 1 | 77 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 2 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 16 Day 1: ECOG score 0 | 52 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 28 Day 1: ECOG score 1 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 24 Day 1: ECOG score 0 | 23 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 21 Day 1: ECOG score 0 | 31 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 1 | 87 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 13 Day 1: ECOG score 1 | 46 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 7 Day 1: ECOG score 0 | 95 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 4 Day 1: ECOG score 1 | 96 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Cycle 15 Day 1: ECOG score 3 | 0 Participants |
Secondary
Part 1 and Part 2: Objective Response Rate (ORR)
ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response.
Time frame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Population: FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Objective Response Rate (ORR) | 63.0 percentage of participants |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Objective Response Rate (ORR) | 50.5 percentage of participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Objective Response Rate (ORR) | 40.3 percentage of participants |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Objective Response Rate (ORR) | 65.9 percentage of participants |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Objective Response Rate (ORR) | 50.0 percentage of participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Objective Response Rate (ORR) | 50.4 percentage of participants |
Secondary
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
FACT-M:melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items,not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.
Time frame: Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Population: FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | NA months |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | 30.5 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | 22.1 months |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | NA months |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | NA months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale | 20.5 months |
Secondary
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from not at all to very much and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score represented better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.
Time frame: Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Population: FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | 23.9 months |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | 14.7 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | 16.6 months |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | 18.4 months |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | 9.5 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) | 11.1 months |
Secondary
Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)
Population: Safety analysis set includes all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | NA months |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | 26.7 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | 18.2 months |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | NA months |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | 10.2 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | 19.2 months |
Secondary
Part 1 and Part 2: Time to Objective Response (TTR)
TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit \[FPFV\] to last patient last visit \[LPLV\] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review.
Time frame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Population: FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1 and Part 2: Time to Objective Response (TTR) | 1.9 months |
| Part 1: Vemurafenib 960 mg BID | Part 1 and Part 2: Time to Objective Response (TTR) | 2.0 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Objective Response (TTR) | 2.1 months |
| Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | Part 1 and Part 2: Time to Objective Response (TTR) | 1.9 months |
| Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Objective Response (TTR) | 1.9 months |
| Part 1 + Part 2: LGX818 300 mg | Part 1 and Part 2: Time to Objective Response (TTR) | 1.9 months |
Secondary
Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03
Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to \>=grade 3.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, 'Number analyzed' signifies number of participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Lymphocytes (hyper) | 14 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Gamma-glutamyl transferase | 43 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Alanine aminotransferase | 15 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Sodium (hypo) | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Hemoglobin (hypo) | 19 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Aspartate aminotransferase | 12 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Phosphate (hypo) | 18 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Creatinine | 35 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Bilirubin | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Neutrophils (hypo) | 14 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Corrected Calcium (hyper) | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Creatine (phospho)kinase | 32 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Potassium (hyper) | 6 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Corrected Calcium (hypo) | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Magnesium (hyper) | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Platelets (hypo) | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Lymphocytes (hypo) | 20 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Magnesium (hypo) | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Leukocytes (hypo) | 5 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Prothrombin international normalized ratio increased | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Glucose serum fasting (hyper) | 20 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Albumin (hypo) | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Potassium (hypo) | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Glucose serum fasting (hypo) | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Alkaline phosphatase | 6 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Creatinine | 15 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Hemoglobin (hypo) | 11 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Prothrombin international normalized ratio increased | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Lymphocytes (hypo) | 15 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Lymphocytes (hyper) | 11 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Neutrophils (hypo) | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Platelets (hypo) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Leukocytes (hypo) | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Albumin (hypo) | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Alkaline phosphatase | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Alanine aminotransferase | 8 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Aspartate aminotransferase | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Bilirubin | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Creatine (phospho)kinase | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Corrected Calcium (hypo) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Corrected Calcium (hyper) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Gamma-glutamyl transferase | 29 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Glucose serum fasting (hypo) | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Glucose serum fasting (hyper) | 12 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Magnesium (hypo) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Magnesium (hyper) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Phosphate (hypo) | 25 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Potassium (hypo) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Potassium (hyper) | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Sodium (hypo) | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Gamma-glutamyl transferase | 15 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Albumin (hypo) | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Hemoglobin (hypo) | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Glucose serum fasting (hypo) | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Leukocytes (hypo) | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Potassium (hypo) | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Glucose serum fasting (hyper) | 12 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Platelets (hypo) | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Prothrombin international normalized ratio increased | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Magnesium (hypo) | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Neutrophils (hypo) | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Sodium (hypo) | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Magnesium (hyper) | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Lymphocytes (hyper) | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Creatine (phospho)kinase | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Potassium (hyper) | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Corrected Calcium (hypo) | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Bilirubin | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Phosphate (hypo) | 35 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Corrected Calcium (hyper) | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Aspartate aminotransferase | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Alanine aminotransferase | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Creatinine | 48 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Alkaline phosphatase | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 | Lymphocytes (hypo) | 41 Participants |
Secondary
Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Rash | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Skin infections | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | PPE syndrome | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Photosensitivity | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Nail disorders | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Severe cutaneous adverse reactions | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Severe cutaneous adverse reactions | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Rash | 10 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Photosensitivity | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Nail disorders | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Skin infections | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | PPE syndrome | 26 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Skin infections | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | PPE syndrome | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Severe cutaneous adverse reactions | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Photosensitivity | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Rash | 25 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Nail disorders | 0 Participants |
Secondary
Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values
Newly occurring notable ECG values were reported for QT (millisecond \[ms\]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (\>) 450, New \>480, New \>500, Increase from baseline \>30, Increase from baseline \>60. Heart rate: New \<60, New \>100 was considered as newly occurring notable value.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here Overall Number of Participants analyzed signifies number of participants evaluable for this outcome measure and 'Number analyzed' signifies number of participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: Increase >60 ms | 11 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: Increase >60 ms | 10 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: Increase >60 ms | 27 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: Increase >30 ms | 105 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >450 ms | 25 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >500 ms | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: Increase >30 ms | 47 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >480 ms | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >480 ms | 5 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >500 ms | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Heart rate: New <100 bpm | 14 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >480 ms | 12 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >500 ms | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Heart rate: New <60 bpm | 58 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >450 ms | 47 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: Increase >30 ms | 50 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >450 ms | 23 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: Increase >30 ms | 74 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: Increase >30 ms | 68 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: Increase >60 ms | 19 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >450 ms | 15 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >480 ms | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >500 ms | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: Increase >30 ms | 56 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: Increase >60 ms | 7 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >450 ms | 39 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >480 ms | 7 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >500 ms | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: Increase >60 ms | 15 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >450 ms | 76 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >480 ms | 23 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >500 ms | 10 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Heart rate: New <60 bpm | 37 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Heart rate: New <100 bpm | 23 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: Increase >60 ms | 24 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: Increase >60 ms | 14 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >500 ms | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Heart rate: New <100 bpm | 18 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >450 ms | 65 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >480 ms | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | Heart rate: New <60 bpm | 16 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >480 ms | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: New >450 ms | 17 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QT: Increase >30 ms | 81 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >480 ms | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: New >500 ms | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >500 ms | 3 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: New >450 ms | 42 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: Increase >60 ms | 10 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcB: Increase >30 ms | 78 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values | QTcF: Increase >30 ms | 76 Participants |
Secondary
Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury \[mmHg\]): less than or equal to (\<=) 90 mmHg with decrease from baseline of greater than or equal to (\>=) 20 mmHg/\>= 160 mmHg with increase from baseline of \>=20 mmHg. Low/high diastolic blood pressure (DBP) \[mmHg\]: \<= 50 mmHg with decrease from baseline of \>=15 mmHg/\>=100 mmHg with increase from baseline of \>=15 mmHg. Low/high Pulse rate: \<=50 beats per minute (bpm) with decrease from baseline of \>=15 bpm/\>= 120 bpm with increase from baseline of \>=15 bpm. Low/high Weight \[kilogram\]: \>=20 percent (%) decrease from baseline/\>= 10% increase from baseline. Low/high Body temperature degree Celsius (C): \<= 36 degree C/\>= 37.5 degree C.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable at specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): High | 44 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): Low | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): High | 27 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (degree C): High | 19 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (degree C): Low | 76 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): Low | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): High | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): High | 23 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): Low | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): Low | 9 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): Low | 8 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): High | 7 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): Low | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): High | 10 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): Low | 7 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (degree C): High | 11 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): High | 14 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): High | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (degree C): Low | 74 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): Low | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (degree C): Low | 57 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): High | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): Low | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): Low | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): High | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): Low | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): High | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): Low | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (degree C): High | 17 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): High | 31 Participants |
Secondary
Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | RVO | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Retinopathy excluding RVO | 5 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Uveitis-type events | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | RVO | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Retinopathy excluding RVO | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Uveitis-type events | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Retinopathy excluding RVO | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Uveitis-type events | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | RVO | 0 Participants |
Secondary
Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline \>=10% and \< 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline \>=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 3 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 0 | 127 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 2 | 56 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Missing | 6 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 3 | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 0 | 161 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 2 | 17 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Missing | 10 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Missing | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 0 | 161 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 3 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 2 | 16 Participants |
Secondary
Part 1: Overall Survival (OS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a death had not been observed by the date of analysis cutoff, OS was censored at the date of last contact.
Time frame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
Secondary
Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported.
Time frame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Participants with AEs | 98.4 percentage of participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Participants with SAEs | 34.4 percentage of participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Participants with AEs | 99.5 percentage of participants |
| Part 1: Vemurafenib 960 mg BID | Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Participants with SAEs | 34.9 percentage of participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Participants with AEs | 99.5 percentage of participants |
| Part 1 + Part 2: LGX818 300 mg | Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Participants with SAEs | 37.1 percentage of participants |
Secondary
Part 1: Plasma Concentrations of LGX 818
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Population: Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose | 18.6 nanogram per milliliter | Standard Deviation 125 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 0.5 hours post dose | 1640 nanogram per milliliter | Standard Deviation 2400 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 1.5 hours post dose | 6860 nanogram per milliliter | Standard Deviation 3680 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 4 to 8 hours post dose | 3400 nanogram per milliliter | Standard Deviation 2010 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of LGX 818 | Cycle 2 Day 1: pre-dose | 119 nanogram per milliliter | Standard Deviation 468 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of LGX 818 | Cycle 3 Day 1: pre-dose | 150 nanogram per milliliter | Standard Deviation 697 |
| Part 1: Vemurafenib 960 mg BID | Part 1: Plasma Concentrations of LGX 818 | Cycle 2 Day 1: pre-dose | 73.6 nanogram per milliliter | Standard Deviation 405 |
| Part 1: Vemurafenib 960 mg BID | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose | 58.1 nanogram per milliliter | Standard Deviation 513 |
| Part 1: Vemurafenib 960 mg BID | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 4 to 8 hours post dose | 1850 nanogram per milliliter | Standard Deviation 925 |
| Part 1: Vemurafenib 960 mg BID | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 0.5 hours post dose | 1190 nanogram per milliliter | Standard Deviation 1790 |
| Part 1: Vemurafenib 960 mg BID | Part 1: Plasma Concentrations of LGX 818 | Cycle 3 Day 1: pre-dose | 53.8 nanogram per milliliter | Standard Deviation 256 |
| Part 1: Vemurafenib 960 mg BID | Part 1: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 1.5 hours post dose | 4090 nanogram per milliliter | Standard Deviation 2100 |
Secondary
Part 1: Plasma Concentrations of MEK162
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Population: Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of MEK162 | Cycle 1 Day 1: pre-dose | 2.95 nanogram per milliliter | Standard Deviation 30.7 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of MEK162 | Cycle 1 Day 1: 0.5 hours post dose | 426 nanogram per milliliter | Standard Deviation 410 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of MEK162 | Cycle 1 Day 1: 1.5 hours post dose | 832 nanogram per milliliter | Standard Deviation 527 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of MEK162 | Cycle 1 Day 1: 4 to 8 hours post dose | 330 nanogram per milliliter | Standard Deviation 226 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of MEK162 | Cycle 2 Day 1: pre-dose | 81.0 nanogram per milliliter | Standard Deviation 106 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 1: Plasma Concentrations of MEK162 | Cycle 3 Day 1: pre-dose | 68.1 nanogram per milliliter | Standard Deviation 101 |
Secondary
Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0
Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.0 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to \>=grade 3.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, 'Number analyzed' signifies number of participants evaluable for specified rows. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Prothrombin international normalized ratio increased | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Glucose serum fasting (hyper) | 27 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Platelets (hypo) | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Magnesium (hypo) | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Magnesium (hyper) | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Phosphate (hypo) | 26 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Leukocytes (hypo) | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Potassium (hypo) | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Sodium (hyper) | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Bilirubin | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Potassium (hyper) | 8 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Hemoglobin (hypo) | 16 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Albumin (hypo) | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Sodium (hypo) | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Lymphocytes (hypo) | 28 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Alkaline phosphatase (hyper) | 11 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Alanine aminotransferase | 18 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Lymphocytes (hyper) | 11 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Aspartate aminotransferase | 15 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Creatine kinase | 40 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Corrected Calcium (hypo) | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Creatinine | 44 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Neutrophils (hypo) | 19 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Gamma-glutamyl transferase | 38 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Glucose serum fasting (hypo) | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Albumin (hypo) | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Creatine kinase | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Glucose serum fasting (hyper) | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Sodium (hyper) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Lymphocytes (hypo) | 10 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Magnesium (hypo) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Platelets (hypo) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Alkaline phosphatase (hyper) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Magnesium (hyper) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Prothrombin international normalized ratio increased | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Hemoglobin (hypo) | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Phosphate (hypo) | 8 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Glucose serum fasting (hypo) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Alanine aminotransferase | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Potassium (hypo) | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Gamma-glutamyl transferase | 9 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Leukocytes (hypo) | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Aspartate aminotransferase | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Corrected Calcium (hypo) | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Creatinine | 11 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Sodium (hypo) | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Potassium (hyper) | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Bilirubin | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Lymphocytes (hyper) | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Neutrophils (hypo) | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Potassium (hypo) | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Sodium (hyper) | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Hemoglobin (hypo) | 16 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Prothrombin international normalized ratio increased | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Lymphocytes (hypo) | 25 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Lymphocytes (hyper) | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Neutrophils (hypo) | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Platelets (hypo) | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Leukocytes (hypo) | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Albumin (hypo) | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Corrected Calcium (hypo) | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Alkaline phosphatase (hyper) | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Alanine aminotransferase | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Bilirubin | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Creatine kinase | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Creatinine | 26 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Gamma-glutamyl transferase | 38 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Glucose serum fasting (hypo) | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Glucose serum fasting (hyper) | 17 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Magnesium (hypo) | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Magnesium (hyper) | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Phosphate (hypo) | 33 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Aspartate aminotransferase | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Potassium (hyper) | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 | Sodium (hypo) | 3 Participants |
Secondary
Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported are reported in this outcome measure.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set includes all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Rash | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Skin infection | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | PPE syndrome | 1 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Photosensitivity | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Nail disorders | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Severe cutaneous adverse reactions | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Severe cutaneous adverse reactions | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Rash | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Photosensitivity | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Nail disorders | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Skin infection | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | PPE syndrome | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Skin infection | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | PPE syndrome | 30 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Severe cutaneous adverse reactions | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Photosensitivity | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Rash | 13 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Nail disorders | 0 Participants |
Secondary
Part 2: Number of Participants With Newly Occurring Notable ECG Values
Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New \>450, New \>480, New \>500, increase from baseline \>30, Increase from baseline \>60. Heart rate: New \< 60, New \>100 was considered as newly occurring notable value.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable at specified rows. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 500 | 10 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 450 | 36 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): Increase from baseline > 30 | 132 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): Increase from baseline > 30 | 69 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 500 | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | Heart rate (bpm): New > 100 | 8 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): Increase from baseline > 60 | 22 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 500 | 2 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | Heart rate (bpm): New < 60 | 82 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): Increase from baseline > 60 | 13 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 480 | 9 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 450 | 70 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): Increase from baseline > 30 | 59 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 450 | 34 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 480 | 23 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 480 | 11 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): Increase from baseline > 60 | 34 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 450 | 28 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 450 | 11 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 480 | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 500 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): Increase from baseline > 60 | 7 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 480 | 6 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 500 | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): Increase from baseline > 30 | 24 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): Increase from baseline > 60 | 8 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | Heart rate (bpm): New < 60 | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | Heart rate (bpm): New > 100 | 10 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): Increase from baseline > 30 | 27 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): Increase from baseline > 60 | 6 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 450 | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 480 | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 500 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): Increase from baseline > 30 | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): Increase from baseline > 30 | 95 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 480 | 29 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 500 | 2 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): Increase from baseline > 60 | 25 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 450 | 104 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 450 | 50 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 450 | 20 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 500 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): Increase from baseline > 60 | 14 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): Increase from baseline > 60 | 23 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QT (ms): New > 480 | 6 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | Heart rate (bpm): New < 60 | 42 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): Increase from baseline > 30 | 98 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): New > 480 | 12 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | Heart rate (bpm): New > 100 | 33 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcB (ms): New > 500 | 11 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notable ECG Values | QTcF (ms): Increase from baseline > 30 | 76 Participants |
Secondary
Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (\<=) 90 mmHg with decrease from baseline of greater than or equal to (\>=) 20 mmHg/\>= 160 mmHg with increase from baseline of \>=20 mmHg, Low/high diastolic blood pressure (DBP) \[mmHg\]: \<=50 mmHg with decrease from baseline of \>=15 mmHg/\>=100 mmHg with increase from baseline of \>=15 mmHg, Low/high pulse rate \[bpm\]: \<=50 bpm with decrease from baseline of \>=15 bpm/\>=120 bpm with increase from baseline of \>=15 bpm, Low/high weight (kg): \>=20 % decrease from baseline/\>= 10% increase from baseline Low/high Body temperature degree C): \<= 36°C/\>= 37.5 degree C.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable at specified rows. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): High | 41 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): Low | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): High | 40 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): Low | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): High | 7 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): Low | 10 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (°C): Low | 120 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (°C): High | 14 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): High | 46 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): Low | 11 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): High | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): Low | 1 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (°C): High | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): Low | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (°C): Low | 22 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): High | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): High | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): Low | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): High | 3 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): Low | 1 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (°C): Low | 96 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): Low | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): High | 17 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Systolic Blood Pressure (mmHg): Low | 8 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): High | 7 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Diastolic Blood Pressure (mmHg): Low | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): High | 11 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Weight (kg): Low | 9 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Body temperature (°C): High | 16 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs | Sitting Pulse Rate (bpm): High | 10 Participants |
Secondary
Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set includes all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | RVO | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Retinopathy excluding RVO | 4 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Uveitis-type events | 4 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | RVO | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Retinopathy excluding RVO | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Uveitis-type events | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Retinopathy excluding RVO | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | Uveitis-type events | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03 | RVO | 1 Participants |
Secondary
Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline \>=10% and \< 20%;Grade 3: LVEF between 20% and 39% or absolute reduction from baseline \>=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 4 | 0 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 3 | 3 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 0 | 181 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 2 | 71 Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Missing | 2 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 3 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 0 | 74 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 2 | 5 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 4 | 0 Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Missing | 5 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Missing | 15 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 4 | 0 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 0 | 235 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 3 | 4 Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade | Grade 2 | 22 Participants |
Secondary
Part 2: Overall Survival (OS)
Time frame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
Secondary
Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported.
Time frame: Baseline up to 30 days after last dose of study drug (up to 36 months)
Population: Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | AEs | 98.1 percentage of Participants |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | SAEs | 29.2 percentage of Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | AEs | 96.4 percentage of Participants |
| Part 1: Vemurafenib 960 mg BID | Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | SAEs | 29.8 percentage of Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | AEs | 98.6 percentage of Participants |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | SAEs | 33.3 percentage of Participants |
Secondary
Part 2: Plasma Concentrations of LGX 818
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Population: Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, Overall Number of Participants Analyzed =number of participants evaluable for this outcome measure and Number analyzed =participants evaluable at each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of LGX 818 | Cycle 2 Day 1: pre-dose | 121 nanogram per milliliter | Standard Deviation 483 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose | 5.02 nanogram per milliliter | Standard Deviation 77.8 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of LGX 818 | Cycle 3 Day 1: pre-dose | 74.1 nanogram per milliliter | Standard Deviation 322 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 4 to 8 hours post dose | 2420 nanogram per milliliter | Standard Deviation 1270 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 0.5 hours post dose | 1360 nanogram per milliliter | Standard Deviation 2000 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 1.5 hours post dose | 4390 nanogram per milliliter | Standard Deviation 2380 |
| Part 1: Vemurafenib 960 mg BID | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 1.5 hours post dose | 4310 nanogram per milliliter | Standard Deviation 2570 |
| Part 1: Vemurafenib 960 mg BID | Part 2: Plasma Concentrations of LGX 818 | Cycle 2 Day 1: pre-dose | 29.5 nanogram per milliliter | Standard Deviation 99.9 |
| Part 1: Vemurafenib 960 mg BID | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 4 to 8 hours post dose | 2250 nanogram per milliliter | Standard Deviation 1170 |
| Part 1: Vemurafenib 960 mg BID | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 0.5 hours post dose | 1370 nanogram per milliliter | Standard Deviation 2170 |
| Part 1: Vemurafenib 960 mg BID | Part 2: Plasma Concentrations of LGX 818 | Cycle 3 Day 1: pre-dose | 79.5 nanogram per milliliter | Standard Deviation 291 |
| Part 1: Vemurafenib 960 mg BID | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose | 0.0145 nanogram per milliliter | Standard Deviation 0.13 |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Plasma Concentrations of LGX 818 | Cycle 3 Day 1: pre-dose | 60.6 nanogram per milliliter | Standard Deviation 265 |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: pre-dose | 39.7 nanogram per milliliter | Standard Deviation 424 |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 0.5 hours post dose | 1250 nanogram per milliliter | Standard Deviation 1910 |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 4 to 8 hours post dose | 1980 nanogram per milliliter | Standard Deviation 1020 |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Plasma Concentrations of LGX 818 | Cycle 2 Day 1: pre-dose | 60.1 nanogram per milliliter | Standard Deviation 342 |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Plasma Concentrations of LGX 818 | Cycle 1 Day 1: 1.5 hours post dose | 4170 nanogram per milliliter | Standard Deviation 2290 |
Secondary
Part 2: Plasma Concentrations of MEK162
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Population: Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of MEK162 | Cycle 1 Day 1: pre-dose | 1.68 nanogram per milliliter | Standard Deviation 24.3 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of MEK162 | Cycle 1 Day 1: 0.5 hours post dose | 366 nanogram per milliliter | Standard Deviation 347 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of MEK162 | Cycle 1 Day 1: 1.5 hours post dose | 642 nanogram per milliliter | Standard Deviation 337 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of MEK162 | Cycle 1 Day 1: 4 to 8 hours post dose | 287 nanogram per milliliter | Standard Deviation 175 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of MEK162 | Cycle 2 Day 1: pre-dose | 72.3 nanogram per milliliter | Standard Deviation 62.6 |
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Plasma Concentrations of MEK162 | Cycle 3 Day 1: pre-dose | 73.2 nanogram per milliliter | Standard Deviation 89 |
Secondary
Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2.
Time frame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
Population: FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group | 12.9 months |
| Part 1: Vemurafenib 960 mg BID | Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group | 7.4 months |
| Part 1 + Part 2: LGX818 300 mg | Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group | 9.2 months |