Hematologic Malignancies, Solid Tumor
Conditions
Brief summary
The purpose of this signal seeking study is to determine whether treatment with LGX818 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study
Interventions
DRUGLGX818
LGX818 will be dosed on a flat scale of 300 mg (e.g., 3 x 100 mg capsules) once daily on a continuous dosing cycle. A complete treatment cycle is defined as 28 days. There will be no breaks between dosing cycles.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has a confirmed diagnosis of a select solid tumor (except with a primary diagnosis of melanoma and colorectal cancer (CRC)) or hematologic malignancies and is in need of treatment because of progression or relapse. * Patient's tumor has been evaluated and pre-identified as having a tumor with a BRAFV600 mutation at a CLIA certified laboratory. * Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission. * Patient must have progressive and measurable disease per RECIST 1.1. or other appropriate hematological response criteria. * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Exclusion criteria
* Patient has received prior treatment with LGX818. * Patients with Central Nerve System (CNS) metastasis or leptomeningeal carcinomatosis. * Patient has received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug. * Patients with acute or chronic pancreatitis. * Patients with impaired cardiac function or clinically significant cardiac diseases. * Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Up to 13.3 months | CBR for solid tumors was defined as percentage of participants with complete response (CR) or partial response (PR), or stable disease (SD) for greater than or equal to (\>=) 16 weeks. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1 | From the date of first dose until the first documentation of PD, relapse, censored date or death, whichever occurred first (maximum up to 13.3 months) | PFS for solid tumors was defined as the time from the date of first dose of study drug to the date of first documented disease progression (PD) or relapse or death due to any cause within 30 days of the last dose. 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. Participants who had no event were censored at the date of last adequate tumor assessment. |
| Overall Survival (OS) for Solid Tumors | From date of the first dose until the date of death, censored date (maximum up to 13.3 months) | OS for solid tumors was defined as the time from the date of first dose of study drug to the date of death due to any cause. For participants who were alive at the time of analysis, the data was censored at the date of last contact. |
| Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1 | From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 months) | DOR for solid tumors was defined as the time from the first documented response (CR or PR) to the date of first documented PD or relapse or death due to any cause, whichever occurred first. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 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 also demonstrate an absolute increase of at least 5 mm. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 | Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 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, urgent intervention indicated. TEAE was defined as event with onset dates occurring during the on-treatment period. CTCAE Grade 5 (death) was not used in this study. |
| Change From Baseline in Systolic and Diastolic Blood Pressure | Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported. |
| Change From Baseline in Sitting Pulse Rate | Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported. |
| Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1 | From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months) | ORR for solid tumors was defined as the percentage of participants achieving an overall best response of CR or PR as assessed per RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Change From Baseline in Respiratory Rate | Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in respiratory rate in breaths per minute was reported. |
| Change From Baseline in Body Weight | Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in body weight in kilogram (Kg) was reported |
| Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months) | Number of participants with shifts from baseline in hematology and serum chemistry laboratory parameters, were graded and reported as low, normal and high as assessed by Common terminology criteria for adverse events (CTCAE) v4.03. 'Low' refers to participants with values that were below lower limit of normal with no observation above the upper limit of normal; 'High' refers to participants with values that were above the upper limit of normal with no observation below the lower limit of normal; 'Low and High' refers to participants with values that were below the lower limit of normal and values that were above the upper limit of normal. |
| Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in QTcF, QT, QRS, and PR duration were reported. QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization. |
| Change From Baseline in Heart Rate | Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in heart rate in terms of beats per minute was reported. |
| Change From Baseline in Body Temperature | Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation) | Change from baseline in body temperature in degree Celsius was reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LGX818 (Encorafenib) Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Disease progression | 2 |
| Overall Study | Participant/guardian decision | 2 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | LGX818 (Encorafenib) |
|---|---|
| Age, Continuous | 57.6 Years STANDARD_DEVIATION 11.17 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 4 / 12 |
Outcome results
Primary
Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
CBR for solid tumors was defined as percentage of participants with complete response (CR) or partial response (PR), or stable disease (SD) for greater than or equal to (\>=) 16 weeks. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. 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.
Time frame: Up to 13.3 months
Population: The full analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGX818 (Encorafenib) | Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 25 percentage of participants |
Secondary
Change From Baseline in Body Temperature
Change from baseline in body temperature in degree Celsius was reported.
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 12, Day 1 | -0.4 degree Celsius | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Baseline | 36.7 degree Celsius | Standard Deviation 0.3 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 2, Day 1 | -0.1 degree Celsius | Standard Deviation 0.32 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 3, Day 1 | 0.0 degree Celsius | Standard Deviation 0.25 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 4, Day 1 | -0.3 degree Celsius | Standard Deviation 0.13 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 5, Day 1 | 0.0 degree Celsius | Standard Deviation 0.13 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 6, Day 1 | -0.4 degree Celsius | Standard Deviation 0.36 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 7, Day 1 | -0.4 degree Celsius | Standard Deviation 0.42 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 8, Day 1 | -0.4 degree Celsius | Standard Deviation 0.42 |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 9, Day 1 | -0.5 degree Celsius | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 10, Day 1 | -0.5 degree Celsius | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at Cycle 11, Day 1 | -0.8 degree Celsius | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Temperature | Change at End of Treatment | -0.1 degree Celsius | Standard Deviation 0.38 |
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight in kilogram (Kg) was reported
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Baseline | 87.0 Kg | Standard Deviation 21.77 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 2, Day 1 | -3.4 Kg | Standard Deviation 2.48 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 3, Day 1 | -3.4 Kg | Standard Deviation 2.77 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 4, Day 1 | -6.5 Kg | Standard Deviation 3.85 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 5, Day 1 | -5.8 Kg | Standard Deviation 3.96 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 6, Day 1 | -6.0 Kg | Standard Deviation 4.57 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 7, Day 1 | -6.8 Kg | Standard Deviation 5.96 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 8, Day 1 | -6.4 Kg | Standard Deviation 4.81 |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 9, Day 1 | -12.5 Kg | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 10, Day 1 | -10.3 Kg | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 11, Day 1 | -9.4 Kg | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at Cycle 12, Day 1 | -9.0 Kg | — |
| LGX818 (Encorafenib) | Change From Baseline in Body Weight | Change at End of Treatment | -3.7 Kg | Standard Deviation 3.43 |
Secondary
Change From Baseline in Heart Rate
Change from baseline in heart rate in terms of beats per minute was reported.
Time frame: Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at End of Treatment | 2.0 beats per minute | Standard Deviation 10.68 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Baseline | 77.3 beats per minute | Standard Deviation 15.79 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 1, Day 15 | 2.9 beats per minute | Standard Deviation 9.01 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 2, Day 1 | 4.1 beats per minute | Standard Deviation 12.31 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 2, Day 15 | -1.0 beats per minute | Standard Deviation 9.3 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 3, Day 1 | -0.4 beats per minute | Standard Deviation 12.66 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 4, Day 1 | 7.3 beats per minute | Standard Deviation 14.74 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 5, Day 1 | -3.0 beats per minute | Standard Deviation 5.29 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 6, Day 1 | -0.7 beats per minute | Standard Deviation 7.77 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 7, Day 1 | 7.0 beats per minute | Standard Deviation 11.31 |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 8, Day 1 | 27.0 beats per minute | — |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 9, Day 1 | -2.0 beats per minute | — |
| LGX818 (Encorafenib) | Change From Baseline in Heart Rate | Change at Cycle 10, Day 1 | -4.0 beats per minute | — |
Secondary
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration
Change from baseline in QTcF, QT, QRS, and PR duration were reported. QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.
Time frame: Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Baseline | 423.9 milliseconds | Standard Deviation 24.84 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 1, Day 15 | 0.6 milliseconds | Standard Deviation 16.11 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 2, Day 1 | 3.1 milliseconds | Standard Deviation 28.33 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 2, Day 15 | -62.0 milliseconds | Standard Deviation 99.9 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 3, Day 1 | 7.0 milliseconds | Standard Deviation 14.3 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 4, Day 1 | 1.3 milliseconds | Standard Deviation 11.5 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 5, Day 1 | 0.7 milliseconds | Standard Deviation 1.53 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 6, Day 1 | -6.0 milliseconds | Standard Deviation 9.17 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 7, Day 1 | -18.5 milliseconds | Standard Deviation 6.36 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 8, Day 1 | -28.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 9, Day 1 | -36.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at Cycle 10, Day 1 | -26.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QTcF: Change at End of Treatment | 4.5 milliseconds | Standard Deviation 25.69 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Baseline | 394.2 milliseconds | Standard Deviation 36.19 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 1, Day 15 | -4.3 milliseconds | Standard Deviation 18.27 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 2, Day 1 | -2.4 milliseconds | Standard Deviation 29.47 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 2, Day 15 | -47.0 milliseconds | Standard Deviation 79.97 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 3, Day 1 | 6.6 milliseconds | Standard Deviation 30.59 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 4, Day 1 | -6.7 milliseconds | Standard Deviation 25.4 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 5, Day 1 | 5.3 milliseconds | Standard Deviation 11.02 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 6, Day 1 | -6.7 milliseconds | Standard Deviation 24.68 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 7, Day 1 | -33.0 milliseconds | Standard Deviation 29.7 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 8, Day 1 | -78.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 9, Day 1 | -29.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at Cycle 10, Day 1 | -18.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QT: Change at End of Treatment | -0.3 milliseconds | Standard Deviation 20.04 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Baseline | 93.9 milliseconds | Standard Deviation 12.75 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 1, Day 15 | -2.3 milliseconds | Standard Deviation 4.68 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 2, Day 1 | -1.1 milliseconds | Standard Deviation 13.5 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 2, Day 15 | 0.6 milliseconds | Standard Deviation 6.31 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 3, Day 1 | -2.4 milliseconds | Standard Deviation 2.61 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 4, Day 1 | -5.0 milliseconds | Standard Deviation 3.61 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 5, Day 1 | -3.3 milliseconds | Standard Deviation 3.06 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 6, Day 1 | 0.0 milliseconds | Standard Deviation 4 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 7, Day 1 | -5.0 milliseconds | Standard Deviation 1.41 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 8, Day 1 | -8.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Baseline | 145.8 milliseconds | Standard Deviation 25.13 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 9, Day 1 | 5.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at Cycle 10, Day 1 | 6.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | QRS: Change at End of Treatment | -6.1 milliseconds | Standard Deviation 6.01 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 1, Day 15 | -7.3 milliseconds | Standard Deviation 19.6 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 2, Day 1 | -7.4 milliseconds | Standard Deviation 26.5 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 2, Day 15 | 1.2 milliseconds | Standard Deviation 11.37 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 3, Day 1 | -0.6 milliseconds | Standard Deviation 19.59 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 4, Day 1 | -6.0 milliseconds | Standard Deviation 2 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 5, Day 1 | 7.3 milliseconds | Standard Deviation 16.29 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 6, Day 1 | 2.7 milliseconds | Standard Deviation 21.39 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 7, Day 1 | 10.0 milliseconds | Standard Deviation 22.63 |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 8, Day 1 | -14.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 9, Day 1 | -13.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at Cycle 10, Day 1 | -8.0 milliseconds | — |
| LGX818 (Encorafenib) | Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration | PR: Change at End of Treatment | -6.9 milliseconds | Standard Deviation 21.96 |
Secondary
Change From Baseline in Respiratory Rate
Change from baseline in respiratory rate in breaths per minute was reported.
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Baseline | 17.6 breaths per minute | Standard Deviation 1.31 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 2, Day 1 | 0.0 breaths per minute | Standard Deviation 1.41 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 3, Day 1 | 2.0 breaths per minute | Standard Deviation 4.47 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 4, Day 1 | -1.0 breaths per minute | Standard Deviation 1.15 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 5, Day 1 | -0.5 breaths per minute | Standard Deviation 1 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 6, Day 1 | 0.0 breaths per minute | Standard Deviation 2 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 7, Day 1 | 0.7 breaths per minute | Standard Deviation 1.15 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 8, Day 1 | -1.0 breaths per minute | Standard Deviation 1.41 |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 9, Day 1 | 0.0 breaths per minute | — |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 10, Day 1 | 0.0 breaths per minute | — |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 11, Day 1 | 0.0 breaths per minute | — |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at Cycle 12, Day 1 | 1.0 breaths per minute | — |
| LGX818 (Encorafenib) | Change From Baseline in Respiratory Rate | Change at End of Treatment | -0.1 breaths per minute | Standard Deviation 1.76 |
Secondary
Change From Baseline in Sitting Pulse Rate
Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported.
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 11, Day 1 | -19.0 bpm | — |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Baseline | 84.8 bpm | Standard Deviation 18.17 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 2, Day 1 | 4.9 bpm | Standard Deviation 8.18 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 3, Day 1 | -1.2 bpm | Standard Deviation 18.67 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 4, Day 1 | -19.0 bpm | Standard Deviation 23.86 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 5, Day 1 | -5.0 bpm | Standard Deviation 4.24 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 6, Day 1 | -10.3 bpm | Standard Deviation 8.33 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 7, Day 1 | -4.3 bpm | Standard Deviation 16.86 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 8, Day 1 | -1.0 bpm | Standard Deviation 42.43 |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 9, Day 1 | -24.0 bpm | — |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 10, Day 1 | -25.0 bpm | — |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at Cycle 12, Day 1 | -23.0 bpm | — |
| LGX818 (Encorafenib) | Change From Baseline in Sitting Pulse Rate | Change at End of Treatment | -2.7 bpm | Standard Deviation 9.33 |
Secondary
Change From Baseline in Systolic and Diastolic Blood Pressure
Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported.
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Baseline | 129.4 mmHg | Standard Deviation 17.33 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 2, Day 1 | 2.4 mmHg | Standard Deviation 4.34 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 3, Day 1 | 4.0 mmHg | Standard Deviation 23.56 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 4, Day 1 | -0.3 mmHg | Standard Deviation 14.52 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 5, Day 1 | 7.8 mmHg | Standard Deviation 11.32 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 6, Day 1 | -5.3 mmHg | Standard Deviation 18.01 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 7, Day 1 | 0.0 mmHg | Standard Deviation 12.49 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 8, Day 1 | 1.5 mmHg | Standard Deviation 4.95 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 9, Day 1 | 2.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 10, Day 1 | 9.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 11, Day 1 | 10.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at Cycle 12, Day 1 | 15.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Change at End of Treatment | 8.7 mmHg | Standard Deviation 18.95 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Baseline | 78.1 mmHg | Standard Deviation 9.33 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 2, Day 1 | -0.1 mmHg | Standard Deviation 8.46 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 3, Day 1 | 1.4 mmHg | Standard Deviation 11.26 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 4, Day 1 | -1.3 mmHg | Standard Deviation 5.62 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 5, Day 1 | -0.5 mmHg | Standard Deviation 4.12 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 6, Day 1 | -0.7 mmHg | Standard Deviation 8.33 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 7, Day 1 | 1.7 mmHg | Standard Deviation 9.71 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 8, Day 1 | 1.0 mmHg | Standard Deviation 4.24 |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 9, Day 1 | 0.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 10, Day 1 | 9.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 11, Day 1 | 5.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at Cycle 12, Day 1 | 0.0 mmHg | — |
| LGX818 (Encorafenib) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Change at End of Treatment | 4.7 mmHg | Standard Deviation 12.12 |
Secondary
Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1
DOR for solid tumors was defined as the time from the first documented response (CR or PR) to the date of first documented PD or relapse or death due to any cause, whichever occurred first. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 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 also demonstrate an absolute increase of at least 5 mm.
Time frame: From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 months)
Population: Data for this outcome measure was not analyzed due to low overall response rate among participants.
Secondary
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities
Number of participants with shifts from baseline in hematology and serum chemistry laboratory parameters, were graded and reported as low, normal and high as assessed by Common terminology criteria for adverse events (CTCAE) v4.03. 'Low' refers to participants with values that were below lower limit of normal with no observation above the upper limit of normal; 'High' refers to participants with values that were above the upper limit of normal with no observation below the lower limit of normal; 'Low and High' refers to participants with values that were below the lower limit of normal and values that were above the upper limit of normal.
Time frame: Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Lactate Dehydrogenase, High | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Serum Total Protein, Low | 3 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Serum Total Protein, Normal | 8 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Serum Total Protein, High | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Low-Density Lipoprotein, Low | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Low-Density Lipoprotein, Normal | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Low-Density Lipoprotein, High | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | High-Density Lipoprotein, Low | 6 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | High-Density Lipoprotein, Normal | 4 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | High-Density Lipoprotein, High | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Thyroid-Stimulating Hormone, Low | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Thyroid-Stimulating Hormone, Normal | 6 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Thyroid-Stimulating Hormone, High | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | T3, Low | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | T3, Normal | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | T3, High | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | T4, Low | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | T4, Normal | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | T4, High | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Red Blood Cell Count, Low | 5 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Red Blood Cell Count, Normal | 6 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Red Blood Cell Count, High | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Hematocrit, Low | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Hematocrit, Normal | 4 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Hematocrit, High | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Eosinophils, Low | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Eosinophils, Normal | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Eosinophils, High | 3 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Basophils, Low | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Basophils, Normal | 9 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Basophils, High | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Monocytes, Low | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Monocytes, Normal | 3 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Monocytes, High | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Neutrophils, Low | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Neutrophils, Normal | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Neutrophils, High | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Lymphocytes, Low | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Lymphocytes, Normal | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Lymphocytes, High | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Blood Urea Nitrogen, Low | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Blood Urea Nitrogen, Normal | 8 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Blood Urea Nitrogen, High | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Bicarbonate, Low | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Bicarbonate, Normal | 7 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Bicarbonate, High | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Lactate Dehydrogenase, Low | 1 Participants |
| LGX818 (Encorafenib) | Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities | Lactate Dehydrogenase, Normal | 7 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 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, urgent intervention indicated. TEAE was defined as event with onset dates occurring during the on-treatment period. CTCAE Grade 5 (death) was not used in this study.
Time frame: Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months)
Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LGX818 (Encorafenib) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 | Grade 1 | 0 Participants |
| LGX818 (Encorafenib) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 | Grade 2 | 2 Participants |
| LGX818 (Encorafenib) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 | Grade 3 | 10 Participants |
| LGX818 (Encorafenib) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 | Grade 4 | 0 Participants |
Secondary
Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1
ORR for solid tumors was defined as the percentage of participants achieving an overall best response of CR or PR as assessed per RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months)
Population: The full analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGX818 (Encorafenib) | Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1 | 0 percentage of participants |
Secondary
Overall Survival (OS) for Solid Tumors
OS for solid tumors was defined as the time from the date of first dose of study drug to the date of death due to any cause. For participants who were alive at the time of analysis, the data was censored at the date of last contact.
Time frame: From date of the first dose until the date of death, censored date (maximum up to 13.3 months)
Population: The full analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGX818 (Encorafenib) | Overall Survival (OS) for Solid Tumors | 13.3 months |
Secondary
Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1
PFS for solid tumors was defined as the time from the date of first dose of study drug to the date of first documented disease progression (PD) or relapse or death due to any cause within 30 days of the last dose. 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. Participants who had no event were censored at the date of last adequate tumor assessment.
Time frame: From the date of first dose until the first documentation of PD, relapse, censored date or death, whichever occurred first (maximum up to 13.3 months)
Population: The full analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGX818 (Encorafenib) | Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1 | NA months |