Melanoma and Brain Metastases
Conditions
Keywords
GSK2118436, Metastatic melanoma to the brain, Brain metastases, Braf mutation, Brain neoplasm, BRAF inhibitor
Brief summary
This study is designed to assess the efficacy, pharmacokinetics, safety, and tolerability of an oral, twice daily dose of 150 mg GSK2118436 administered to subjects with BRAF V600E or V600K mutation-positive metastatic melanoma to the brain. Subjects in Cohort A will not have received any local brain therapy, and subjects in Cohort B will have received prior local therapy for brain metastases. Subjects will continue on treatment until disease progression, death, or unacceptable adverse event.
Interventions
DRUGGSK2118436
Subjects in this study receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohort A: * No prior local therapy for brain metastases. * Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 3 weeks prior to first dose of study treatment. * No prophylactic or preventive anti-epileptic therapy. Exception: anti-epileptic therapy indicated in order to prevent neurologic symptoms caused by a pre-existing condition and not related to brain metastasis is allowed. * Cohort B: * Subjects must have received at least one local therapy for brain metastases including but not restricted to brain surgery, Whole Brain Radiotherapy or Stereotactic Radiosurgery (e.g. gamma knife, linear-accelerated-based radiosurgery, charged particles, and CyberKnife). Multiple local therapies or combinations of local therapies are allowed. For subjects receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (\> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For subjects receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated. * Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to first dose of study treatment. * Prophylactic or preventive anti-epileptic therapy is allowed. * General: * Must sign written informed consent. * Must be at least 18 years of age. * Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600E- or V600K-mutation. * Up to two previous treatment regimens for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy. * At least one measurable intracranial target lesion for which all of the following criteria have to be met: * previously untreated or progressive according to RECIST 1.1 (greater than or equal to 20% increase in longest diameter on baseline scan) after previous local therapy * immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy * largest diameter of greater than or equal to 0.5cm but less than or equal to 4 cm as determined by contrast-enhanced MRI * for target lesions (for definition see Section 6.1.1) with diameter of greater than 0.5 cm but less than or equal to 1 cm documented measurement by a neuroradiologist is required. * for all lesions with diameter of greater than or equal to 3 cm but less than or equal to 4 cm documented measurement by a neuroradiologist is required. * Time interval between last day of previous anti-tumour systemic treatment and first dose of GSK2118436: * 14 days elapsed from last treatment with surgery, SRS or gamma knife * 28 days elapsed from last treatment with WBRT * Greater than or equal to 28 days or five half-lives (whichever is longer) have elapsed from last dose of approved or investigational chemo-, cytokine-, immune-, biological-, or vaccine-therapy. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. * Adequate organ function. * Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study. * Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment.
Exclusion criteria
* Neurological symptoms related to brain metastasis. * Previous treatment with a BRAF or MEK inhibitor. * Current or expected use of a prohibited medication during treatment with GSK2118436. * Presence of leptomeningeal disease or primary dural metastases. * Known allergies against contrast agents required for magnetic resonance imaging (MRI) of intracranial lesions. * Current use of therapeutic warfarin. NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted. * Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia. * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. * A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection. * Acute infection requiring intravenous antibiotics * History of another malignancy. Exception: (a) Subjects who have been disease-free for 5 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from melanoma target and non-target lesions are eligible. * Certain cardiac abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator | From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks) | OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PR) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters (e.g., percent change from Baseline). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | From the time of the Baseline assessment until disease progression or end of study treatment (average of 17 weeks) | OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders. |
| Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator | From the time of the Baseline assessment until disease progression or end of study treatment (average of 16 weeks) | OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PF) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters (e.g., percent change from Baseline). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment. |
| Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants | Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 27 weeks) | Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented intracranial disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). |
| Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants | Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 31 weeks) | Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented intracranial disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). |
| Duration of Overall Response for the Subset of V600E Mutation-positive Participants | Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 28 weeks) | Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). |
| Duration of Overall Response for the Subset of V600K Mutation-positive Participants | Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 31 weeks) | Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). |
| Progression-free Survival in V600E Mutation-positive Participants | Time from the first dose of study medication to the earliest of death or progression (average of 23 weeks) | PFS is defined as the time from the first dose of study medication to the earliest of death or progression (at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters \[e.g., percent change from Baseline\]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Progression-free Survival in V600K Mutation-positive Participants | Time from the first dose of study medication to the earliest of death or progression (average of 17 weeks) | PFS is defined as the time from the first dose of study medication to the earliest of death or progression (at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters \[e.g., percent change from Baseline\]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Overall Survival of V600E Mutation-positive Participants | Time from the first dose of study medication until death due to any cause (average of 35 weeks) | Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis. |
| Overall Survival in V600K Mutation-positive Participants | Time from the first dose of study medication until death due to any cause (average of 26 weeks) | Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis. |
| Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | From the time of the Baseline assessment until disease progression or end of study treatment (average of 24 weeks) | OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders. |
| Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | From Screening until the conclusion of the study (up to 103 weeks) | Clinical chemistry data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade (G) 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death related to toxicity. Blood sample was collected for the assessment of glucose, potassium, magnesium, sodium, phosphorus, potassium. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, total bilirubin, albumin, amylase, cholesterol, creatine kinase, gamma glutamyl transferase (GGT), lipase, blood pH, and triglycerides. |
| Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | From Screening until the conclusion of the study (up to 103 weeks) | Blood samples were collected for the assessment of hepatobiliary parameters. ALT=alanine aminotranserase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; BIL=total bilirubin; INR=international normalized ratio; ULN=upper limit of normal. Hepato-cellular injury is defined as (ALT/ULN)/(ALP/ULN) \>=5. |
| Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | From Screening until the conclusion of the study (up to 103 weeks) | Hematology data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe, Grade 4, life threatening, Grade 5, death related to toxicity. Blood sample was collected for the assessment of hemoglobin, white blood cells, and platelet count. |
| Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Baseline; Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic and diastolic blood pressure were measured for all treated participants. |
| Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Baseline; Weeks 4, 12, 20, 28, 40, 52, and 64 | An increase in the QTc interval corrected using Bazett's formula (Bazett's QTc) was recorded for all treated participants. Grade 1 (450-480 milliseconds \[msec\]), Grade 2 (481-500 msec), Grade 3/4 (\>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. |
| Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | Weeks (W) 4 and 12 | Echocardiograms (ECHO) were measured for all treated participants. An echocardiogram test gives information about the structure and function of the heart. LLN=lower limit of normal (determined by the institution). |
| Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | Week 4 (pre-dose and 1-3 hours post-dose) and Weeks 8, 16, 24, and 32 (either pre-dose in the morning or in the afternoon at 4-8 hours post-dose) | Summary statistics were calculated for each time point by cohort. The population pharmacokinetics were determined using a non-linear mixed effects modeling approach after pooling the data with other studies. These results are reported separately. |
| Composite of Pharmacokinetic Parameters of GSK2118436 in a Subset of Participants Receiving Dexamethasone | Day 15 | This outcome measure could not be analyzed because too few participants participated in the dexamethasone study. |
| Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Screening | The BRAF screening assay determines the specific BRAF mutational status (V600 E and K) in participants with metastatic melanoma who may benefit from treatment with GSK2118436. Per RECIST, version 1.1, CR is defined as the disappearance of all lesions. PR is defined as a \>=30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline (BL) sum of the diameters (e.g., percent change from BL). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a \>=20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir \[smallest sum of diameters recorded since treatment start\]). In addition, the sum must have an absolute increase from nadir of 5 millimeters. Not evaluable: cannot be classified by a preceding definition. |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From Screening until the conclusion of the study (up to 103 weeks) | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. |
Countries
Australia, Canada, France, Germany, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GSK2118436 150 mg: No Prior Local Therapy Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events. | 89 |
| GSK2118436 150 mg: Prior Local Therapy Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events. | 83 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 69 | 61 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Study Closed/Terminated | 15 | 17 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | GSK2118436 150 mg: No Prior Local Therapy | GSK2118436 150 mg: Prior Local Therapy | Total |
|---|---|---|---|
| Age, Continuous | 52.3 Years STANDARD_DEVIATION 13.35 | 52.7 Years STANDARD_DEVIATION 13.83 | 52.5 Years STANDARD_DEVIATION 13.55 |
| Race/Ethnicity, Customized Not reported | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 89 participants | 82 participants | 171 participants |
| Sex: Female, Male Female | 24 Participants | 28 Participants | 52 Participants |
| Sex: Female, Male Male | 65 Participants | 55 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 89 | 74 / 83 |
| serious Total, serious adverse events | 26 / 89 | 31 / 83 |
Outcome results
Primary
Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator
OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PR) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters (e.g., percent change from Baseline). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.
Time frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks)
Population: V600E Population: all participants with BRAF V600E mutation-positive melanoma who received at least one dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator | CR | 4 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator | PR | 26 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator | CR | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator | PR | 23 participants |
p-value: <0.000195% CI: [29.3, 52.6]Exact Test
p-value: <0.000195% CI: [25.3, 49.8]Exact Test
Secondary
Composite of Pharmacokinetic Parameters of GSK2118436 in a Subset of Participants Receiving Dexamethasone
This outcome measure could not be analyzed because too few participants participated in the dexamethasone study.
Time frame: Day 15
Secondary
Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants
Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented intracranial disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time frame: Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 27 weeks)
Population: V600E Population. Only the subset of participants who had a complete or partial intracranial response was included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants | 24.1 weeks |
| GSK2118436 150 mg: Prior Local Therapy | Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants | 28.1 weeks |
Secondary
Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants
Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented intracranial disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time frame: Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 31 weeks)
Population: V600K Population. Only the subset of participants who had a complete or partial intracranial response was included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants | 12.4 weeks |
| GSK2118436 150 mg: Prior Local Therapy | Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants | NA weeks |
Secondary
Duration of Overall Response for the Subset of V600E Mutation-positive Participants
Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time frame: Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 28 weeks)
Population: V600E Population. Only the subset of participants who had a complete or partial response was included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Duration of Overall Response for the Subset of V600E Mutation-positive Participants | 27.6 weeks |
| GSK2118436 150 mg: Prior Local Therapy | Duration of Overall Response for the Subset of V600E Mutation-positive Participants | 23.7 weeks |
Secondary
Duration of Overall Response for the Subset of V600K Mutation-positive Participants
Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) until the time of the first documented disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time frame: Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 31 weeks)
Population: V600K Population. Only the subset of participants who had a complete or partial response was included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: Prior Local Therapy | Duration of Overall Response for the Subset of V600K Mutation-positive Participants | 36.1 weeks |
Secondary
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36
Systolic and diastolic blood pressure were measured for all treated participants.
Time frame: Baseline; Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36
Population: ATS Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 8, n=70, 73 | 74.6 millimeters of mercury (mmHg) | Standard Deviation 9.14 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Baseline, n=89, 83 | 126.6 millimeters of mercury (mmHg) | Standard Deviation 16.73 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 20, n=29, 34 | 73.6 millimeters of mercury (mmHg) | Standard Deviation 9.98 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 4, n=81, 78 | 122.2 millimeters of mercury (mmHg) | Standard Deviation 13.68 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 4, n=81, 78 | 74.0 millimeters of mercury (mmHg) | Standard Deviation 10.12 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 8, n=70, 73 | 123.0 millimeters of mercury (mmHg) | Standard Deviation 12.71 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 24, n=22, 25 | 74.7 millimeters of mercury (mmHg) | Standard Deviation 7.87 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 12, 68, 62 | 123.6 millimeters of mercury (mmHg) | Standard Deviation 14.74 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 12, n=68, 62 | 75.2 millimeters of mercury (mmHg) | Standard Deviation 7.7 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 16, n=52, 52 | 124.7 millimeters of mercury (mmHg) | Standard Deviation 17.7 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 28, n=15, 17 | 73.9 millimeters of mercury (mmHg) | Standard Deviation 6.98 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 20, n=29, 34 | 123.7 millimeters of mercury (mmHg) | Standard Deviation 16.02 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Baseline, n=89,83 | 77.7 millimeters of mercury (mmHg) | Standard Deviation 8.78 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 24, n=22, 25 | 126.3 millimeters of mercury (mmHg) | Standard Deviation 17.8 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 32, n=9, 7 | 73.1 millimeters of mercury (mmHg) | Standard Deviation 9.47 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 28, n=15, 17 | 122.2 millimeters of mercury (mmHg) | Standard Deviation 17.03 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 32, n=9, 7 | 122.8 millimeters of mercury (mmHg) | Standard Deviation 14.84 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 16, n=52, 52 | 73.2 millimeters of mercury (mmHg) | Standard Deviation 10.01 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 36, n=2, 1 | 119.5 millimeters of mercury (mmHg) | Standard Deviation 13.44 |
| GSK2118436 150 mg: No Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 36, n=2, 1 | 75.5 millimeters of mercury (mmHg) | Standard Deviation 7.78 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 36, n=2, 1 | 128.0 millimeters of mercury (mmHg) | — |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Baseline, n=89,83 | 77.1 millimeters of mercury (mmHg) | Standard Deviation 9.73 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 4, n=81, 78 | 74.6 millimeters of mercury (mmHg) | Standard Deviation 10.88 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 8, n=70, 73 | 72.7 millimeters of mercury (mmHg) | Standard Deviation 9.54 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 12, n=68, 62 | 74.3 millimeters of mercury (mmHg) | Standard Deviation 11.64 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 16, n=52, 52 | 71.4 millimeters of mercury (mmHg) | Standard Deviation 9.4 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 20, n=29, 34 | 71.7 millimeters of mercury (mmHg) | Standard Deviation 9.67 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 24, n=22, 25 | 72.7 millimeters of mercury (mmHg) | Standard Deviation 9.99 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 28, n=15, 17 | 76.5 millimeters of mercury (mmHg) | Standard Deviation 8.37 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 32, n=9, 7 | 73.6 millimeters of mercury (mmHg) | Standard Deviation 9.64 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Diastolic BP, Week 36, n=2, 1 | 93.0 millimeters of mercury (mmHg) | — |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Baseline, n=89, 83 | 123.9 millimeters of mercury (mmHg) | Standard Deviation 14.17 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 4, n=81, 78 | 121.9 millimeters of mercury (mmHg) | Standard Deviation 15.37 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 8, n=70, 73 | 117.3 millimeters of mercury (mmHg) | Standard Deviation 14.53 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 12, 68, 62 | 120.1 millimeters of mercury (mmHg) | Standard Deviation 14.21 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 16, n=52, 52 | 119.9 millimeters of mercury (mmHg) | Standard Deviation 11.67 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 20, n=29, 34 | 118.9 millimeters of mercury (mmHg) | Standard Deviation 13.51 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 24, n=22, 25 | 120.9 millimeters of mercury (mmHg) | Standard Deviation 16.63 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 32, n=9, 7 | 117.7 millimeters of mercury (mmHg) | Standard Deviation 10.01 |
| GSK2118436 150 mg: Prior Local Therapy | Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 | Systolic BP, Week 28, n=15, 17 | 120.8 millimeters of mercury (mmHg) | Standard Deviation 14.32 |
Secondary
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542
Summary statistics were calculated for each time point by cohort. The population pharmacokinetics were determined using a non-linear mixed effects modeling approach after pooling the data with other studies. These results are reported separately.
Time frame: Week 4 (pre-dose and 1-3 hours post-dose) and Weeks 8, 16, 24, and 32 (either pre-dose in the morning or in the afternoon at 4-8 hours post-dose)
Population: PK Population: participants in the ATS population for whom a PK sample was obtained and analyzed. Only those participants whose samples were available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 4, predose, n=55, 58 | 62.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 4, 1-3 hours (hrs), n=63, 70 | 992.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 8, predose, n=36, 36 | 27.2 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 8, 4-8 hrs, n=19, 25 | 274.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 16, predose, n=26, 23 | 27.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 16, 4-8 hrs, n=11, 18 | 341.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 24, predose, n=14, 10 | 60.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 24, 4-8 hrs, n=5, 12 | 371.2 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 32, predose, n=11, 7 | 38.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 32, 4-8 hrs, n=2, 8 | 227.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 4, predose, n=55, 58 | 31.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 4, 1-3 hrs, n=63, 70 | 688.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 8, predose, n=36, 36 | 46.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 8, 4-8 hrs, n=19, 25 | 335.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 16, predose, n=26, 23 | 45.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 16, 4-8 hrs, n=11, 18 | 434.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 24, predose, n=14, 10 | 97.3 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 24, 4-8 hrs, n=5, 12 | 617.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 32, predose, n=11, 7 | 63.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 32, 4-8 hrs, n=2, 8 | 375.3 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 4, predose, n=55, 58 | 3215.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 4, 1-3 hrs, n=63, 70 | 4272.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 8, predose, n=36, 36 | 3152.0 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 8, 4-8 hrs, n=19, 25 | 4692.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 16, predose, n=26, 23 | 3070.0 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 16, 4-8 hrs, n=11, 18 | 4865.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 24, predose, n=14, 10 | 3026.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 24, 4-8 hrs, n=5, 12 | 3825.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 32, predose, n=11, 7 | 2386.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 32, 4-8 hrs, n=2, 8 | 11225.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 4, predose, n=55, 58 | 317.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 4, 1-3 hrs, n=63, 70 | 351.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 8, predose, n=36, 36 | 324.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 8, 4-8 hrs, n=19, 25 | 305.4 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 16, predose, n=26, 23 | 285.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 16, 4-8 hrs, n=11, 18 | 291.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 24, predose, n=14, 10 | 304.0 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 24, 4-8 hrs, n=5, 12 | 190.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 32, predose, n=11, 2 | 361.2 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: No Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 32, 4-8 hrs, n=2, 8 | 227.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 24, 4-8 hrs, n=5, 12 | 287.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 4, predose, n=55, 58 | 50.2 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 4, predose, n=55, 58 | 3877.4 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 4, 1-3 hours (hrs), n=63, 70 | 810.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 4, predose, n=55, 58 | 323.0 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 8, predose, n=36, 36 | 37.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 4, 1-3 hrs, n=63, 70 | 4500.3 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 8, 4-8 hrs, n=19, 25 | 294.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 16, 4-8 hrs, n=11, 18 | 320.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 16, predose, n=26, 23 | 30.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 8, predose, n=36, 36 | 3250.0 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 16, 4-8 hrs, n=11, 18 | 295.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 4, 1-3 hrs, n=63, 70 | 332.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 24, predose, n=14, 10 | 53.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 8, 4-8 hrs, n=19, 25 | 5447.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 24, 4-8 hrs, n=5, 12 | 226.1 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 32, 4-8 hrs, n=2, 8 | 273.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 32, predose, n=11, 7 | 28.4 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 16, predose, n=26, 23 | 3561.2 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2118436, Week 32, 4-8 hrs, n=2, 8 | 335.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 8, predose, n=36, 36 | 298.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 4, predose, n=55, 58 | 80.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 16, 4-8 hrs, n=11, 18 | 6595.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 4, 1-3 hrs, n=63, 70 | 593.2 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 24, predose, n=14, 10 | 334.0 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 8, predose, n=36, 36 | 74.4 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 24, predose, n=14, 10 | 4199.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 8, 4-8 hrs, n=19, 25 | 310.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 8, 4-8 hrs, n=19, 25 | 320.5 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 16, predose, n=26, 23 | 54.4 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 24, 4-8 hrs, n=5, 12 | 5659.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 16, 4-8 hrs, n=11, 18 | 456.9 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 32, predose, n=11, 2 | 316.3 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 24, predose, n=14, 10 | 103.3 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 32, predose, n=11, 7 | 2451.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 24, 4-8 hrs, n=5, 12 | 357.7 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2167542, Week 16, predose, n=26, 23 | 310.8 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 32, predose, n=11, 7 | 46.6 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2298683, Week 32, 4-8 hrs, n=2, 8 | 6547.4 nanograms per milliliter (ng/mL) |
| GSK2118436 150 mg: Prior Local Therapy | Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 | GSK2285403, Week 32, 4-8 hrs, n=2, 8 | 377.5 nanograms per milliliter (ng/mL) |
Secondary
Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12
Echocardiograms (ECHO) were measured for all treated participants. An echocardiogram test gives information about the structure and function of the heart. LLN=lower limit of normal (determined by the institution).
Time frame: Weeks (W) 4 and 12
Population: ATS Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 4, Left ventricle (LV) ejection fraction < LLN | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 4, LV ejection fraction < normal | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 12, LV ejection fraction < LLN | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 12, LV ejection fraction < normal | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 12, LV ejection fraction < normal | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 4, Left ventricle (LV) ejection fraction < LLN | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 12, LV ejection fraction < LLN | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 | W 4, LV ejection fraction < normal | 0 participants |
Secondary
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Time frame: From Screening until the conclusion of the study (up to 103 weeks)
Population: All Treated Subjects (ATS) Population: all participants who received at least one dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 81 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 26 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 79 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 31 participants |
Secondary
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters
Clinical chemistry data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade (G) 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death related to toxicity. Blood sample was collected for the assessment of glucose, potassium, magnesium, sodium, phosphorus, potassium. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, total bilirubin, albumin, amylase, cholesterol, creatine kinase, gamma glutamyl transferase (GGT), lipase, blood pH, and triglycerides.
Time frame: From Screening until the conclusion of the study (up to 103 weeks)
Population: ATS Population. Only those participants with data available for the indicated parameters were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Glucose (hyperglycemia), AGI, n=165 | 71 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Glucose (hyperglycemia), Increase to G 3, n=165 | 8 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Glucose (hyperglycemia), Increase to G 4, n=165 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Glucose (hypoglycemia), AGI, n=165 | 24 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Glucose (hypoglycemia), Increase to G 3, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Glucose (hypoglycemia), Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Magnesium (hypermagnesemia) AGI, n=165 | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Magnesium (hypermagnesemia), Increase to G 3,n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Magnesium (hypermagnesemia), Increase to G 4,n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Magnesium (hypomagnesemia), AGI, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Magnesium (hypomagnesemia), Increase to G 3, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Magnesium (hypomagnesemia), Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Sodium (hypernatremia), AGI, n=165 | 8 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Sodium (hypernatremia), Increase to G 3, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Sodium (hypernatremia), Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Sodium (hyponatremia), AGI, n=165 | 21 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Sodium (hyponatremia), Increase to G 3, n=165 | 3 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Sodium (hyponatremia), Increase to G. 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Phosphorus inorganic, AGI, n=165 | 53 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Phosphorus inorganic, Increase to G 3, n=165 | 13 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Phosphorus inorganic, Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Potassium (hyperkalemia), AGI, n=165 | 8 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Potassium (hyperkalemia), Increase to G 3, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Potassium (hyperkalemia), Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Potassium (hypokalemia), AGI, n=165 | 17 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Potassium (hypokalemia), Increase to G 3, n=165 | 4 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Potassium (hypokalemia), Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | ALP, AGI, n=165 | 41 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | ALP, Increase to G 3, n=165 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | ALP, Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | AST, AGI, n=165 | 26 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | AST, Increase to G 3, n=165 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | AST, Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | ALT, AGI, n=165 | 27 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | ALT, Increase to G 3, n=165 | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | ALT, Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Creatinine, AGI, n=165 | 10 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Creatinine, Increase to G 3, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Creatinine, Increase to G 4, n=165 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Total bilirubin, AGI, n=163 | 5 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Total bilirubin, Increase to G 3 n=163 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Total bilirubin, Increase to G 4 n=163 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Albumin, AGI, n=27 | 9 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Albumin, Increase to G 3, n=27 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Albumin, Increase to G 4, n=27 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Amylase, AGI, n=16 | 3 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Amylase, Increase to G 3, n=16 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Amylase, Increase to G 4, n=16 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Cholesterol, AGI, n=2 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Cholesterol, Increase to G 3, n=2 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Cholesterol, Increase to G 4, n=2 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Creatine kinase, AGI, n=6 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Creatine kinase, Increase to G 3, n=6 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Creatine kinase, Increase to G 4, n=6 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | GGT, AGI, n=22 | 13 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | GGT, Increase to G 3, n=22 | 4 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | GGT, Increase to G 4, n=22 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Lipase, AGI, n=19 | 10 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Lipase, Increase to G 3, n=19 | 4 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Lipase, Increase to G 4, n=19 | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Blood pH, AGI, n=1 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Blood pH, Increase to G 3, n=1 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Blood pH, Increase to G 4, n=1 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Triglycerides, AGI, n=5 | 3 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Triglycerides, Increase to G 3, n=5 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters | Triglycerides, Increase to G 4, n=5 | 0 participants |
Secondary
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters
Hematology data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe, Grade 4, life threatening, Grade 5, death related to toxicity. Blood sample was collected for the assessment of hemoglobin, white blood cells, and platelet count.
Time frame: From Screening until the conclusion of the study (up to 103 weeks)
Population: ATS Population. Only those participants with data available for the indicated parameters were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (anemia), AGI | 25 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (anemia), Increase to Grade 3 | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (anemia), Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (increased), AGI | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (increased), Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (increased), Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count increased, AGI | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count increased, Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count increased, Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count decreased, AGI | 18 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count decreased, Increase Grade 3 | 4 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count decreased, Increase Grade 4 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Total neutrophils, AGI, | 6 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Total neutrophils, Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Total neutrophils, Increase to Grade 4 | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Platelet count, AGI | 7 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Platelet count, Increase to Grade 3 | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Platelet count, Increase to Grade 4 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | White blood cell count, AGI | 9 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | White blood cell count, Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | White blood cell count, Increase to Grade 4 | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count decreased, Increase Grade 3 | 6 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (anemia), AGI | 81 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | White blood cell count, AGI | 16 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (anemia), Increase to Grade 3 | 3 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count decreased, Increase Grade 4 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (anemia), Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Platelet count, Increase to Grade 3 | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (increased), AGI | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Total neutrophils, AGI, | 11 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (increased), Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | White blood cell count, Increase to Grade 4 | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Hemoglobin (increased), Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Total neutrophils, Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count increased, AGI | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Platelet count, Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count increased, Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Total neutrophils, Increase to Grade 4 | 2 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count increased, Increase to Grade 4 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | White blood cell count, Increase to Grade 3 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Lymphocyte count decreased, AGI | 81 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters | Platelet count, AGI | 9 participants |
Secondary
Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG)
An increase in the QTc interval corrected using Bazett's formula (Bazett's QTc) was recorded for all treated participants. Grade 1 (450-480 milliseconds \[msec\]), Grade 2 (481-500 msec), Grade 3/4 (\>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade.
Time frame: Baseline; Weeks 4, 12, 20, 28, 40, 52, and 64
Population: ATS Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Increase from Baseline to any grade | 11 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Increase from Baseline to Grade 2 | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Increase from Baseline to Grade 3/4 | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Increase from Baseline to any grade | 17 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Increase from Baseline to Grade 2 | 2 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) | Increase from Baseline to Grade 3/4 | 0 participants |
Secondary
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities
Blood samples were collected for the assessment of hepatobiliary parameters. ALT=alanine aminotranserase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; BIL=total bilirubin; INR=international normalized ratio; ULN=upper limit of normal. Hepato-cellular injury is defined as (ALT/ULN)/(ALP/ULN) \>=5.
Time frame: From Screening until the conclusion of the study (up to 103 weeks)
Population: ATS Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Hepato-cellular injury | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >20x ULN ALT or AST | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Bilirubin elevations, >=2x ULN BIL and <2x ULN BIL | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >3x ULN ALT | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Possible HYs Law, >3x ULN ALT, >1.5x ULN INR | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >5x ULN ALT | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >3x ULN ALT or AST | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >8x ULN ALT | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Possible HYs Law, >3x ULN ALT, >=2x ULN BIL | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >20x ULN ALT | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >5x ULN ALT or AST | 1 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >3x ULN ALT, <=3x ULN ALT Baseline | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALP elevations, >=3x ULN ALP | 5 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Bilirubin elevations, >=2x ULN BIL | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALP elevations, >=3x ULN ALP and <3x ULN ALP | 4 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >8x ULN ALT or AST | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALP elevations, >=3x ULN ALP and <3x ULN ALP | 2 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Possible HYs Law, >3x ULN ALT, >1.5x ULN INR | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Possible HYs Law, >3x ULN ALT, >=2x ULN BIL | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Hepato-cellular injury | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Bilirubin elevations, >=2x ULN BIL | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | Bilirubin elevations, >=2x ULN BIL and <2x ULN BIL | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >3x ULN ALT or AST | 4 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >5x ULN ALT or AST | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >8x ULN ALT or AST | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT or AST elevations, >20x ULN ALT or AST | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >3x ULN ALT | 4 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >5x ULN ALT | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >8x ULN ALT | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >20x ULN ALT | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALP elevations, >=3x ULN ALP | 2 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities | ALT elevations, >3x ULN ALT, <=3x ULN ALT Baseline | 4 participants |
Secondary
Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator
OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders.
Time frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 24 weeks)
Population: V600E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | CR | 2 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | PR | 28 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | CR | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | PR | 23 participants |
Secondary
Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator
OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders.
Time frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 17 weeks)
Population: V600K Population: all participants with BRAF V600K mutation-positive melanoma who received at least one dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | CR | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | PR | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | CR | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator | PR | 5 participants |
Secondary
Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator
OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PF) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters (e.g., percent change from Baseline). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.
Time frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 16 weeks)
Population: V600K Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator | CR | 0 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator | PR | 1 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator | CR | 0 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator | PR | 4 participants |
Secondary
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response
The BRAF screening assay determines the specific BRAF mutational status (V600 E and K) in participants with metastatic melanoma who may benefit from treatment with GSK2118436. Per RECIST, version 1.1, CR is defined as the disappearance of all lesions. PR is defined as a \>=30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline (BL) sum of the diameters (e.g., percent change from BL). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a \>=20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir \[smallest sum of diameters recorded since treatment start\]). In addition, the sum must have an absolute increase from nadir of 5 millimeters. Not evaluable: cannot be classified by a preceding definition.
Time frame: Screening
Population: V600EK and THIDEK Population: all enrolled participants who were V600E or V600K mutation positive by the RGI IUO assay
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Partial response | 52 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Progressive disease | 26 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Stable disease | 78 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Not evaluable | 14 participants |
| GSK2118436 150 mg: No Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Complete response | 2 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Not evaluable | 12 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Complete response | 2 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Partial response | 49 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Stable disease | 69 participants |
| GSK2118436 150 mg: Prior Local Therapy | Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response | Progressive disease | 23 participants |
Secondary
Overall Survival in V600K Mutation-positive Participants
Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis.
Time frame: Time from the first dose of study medication until death due to any cause (average of 26 weeks)
Population: V600K Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Overall Survival in V600K Mutation-positive Participants | 3.7 months |
| GSK2118436 150 mg: Prior Local Therapy | Overall Survival in V600K Mutation-positive Participants | 5.0 months |
Secondary
Overall Survival of V600E Mutation-positive Participants
Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis.
Time frame: Time from the first dose of study medication until death due to any cause (average of 35 weeks)
Population: V600E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Overall Survival of V600E Mutation-positive Participants | 6.8 months |
| GSK2118436 150 mg: Prior Local Therapy | Overall Survival of V600E Mutation-positive Participants | 7.6 months |
Secondary
Progression-free Survival in V600E Mutation-positive Participants
PFS is defined as the time from the first dose of study medication to the earliest of death or progression (at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters \[e.g., percent change from Baseline\]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Time from the first dose of study medication to the earliest of death or progression (average of 23 weeks)
Population: V600E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Progression-free Survival in V600E Mutation-positive Participants | 16.1 weeks |
| GSK2118436 150 mg: Prior Local Therapy | Progression-free Survival in V600E Mutation-positive Participants | 16.0 weeks |
Secondary
Progression-free Survival in V600K Mutation-positive Participants
PFS is defined as the time from the first dose of study medication to the earliest of death or progression (at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters \[e.g., percent change from Baseline\]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Time from the first dose of study medication to the earliest of death or progression (average of 17 weeks)
Population: V600K Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2118436 150 mg: No Prior Local Therapy | Progression-free Survival in V600K Mutation-positive Participants | 8.1 weeks |
| GSK2118436 150 mg: Prior Local Therapy | Progression-free Survival in V600K Mutation-positive Participants | 15.6 weeks |