Cancer
Conditions
Keywords
drug-drug interaction, BRAF inhibitor, expansion cohorts, melanoma, dose escalation, MEK inhibitor
Brief summary
This was an open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK2118436 and GSK1120212 in combination. This study was designed in four parts. In Part A, the effect of repeat doses of GSK1120212 on the pharmacokinetics of single dose GSK2118436 was investigated prior to evaluating combination regimens. In Part B, the range of tolerated dose combinations was identified using a dose-escalation procedure. In Part C, different dose combinations of GSK2118436 and GSK1120212 were evaluated, based on results from the dose escalation cohorts. In Part D, the pharmacokinetics and safety of GSK2118436 administered as HPMC capsules alone and in combination with GSK1120212 was evaluated.
Detailed description
During Part A, a cohort of subjects received a single dose of GSK2118436 alone (Day 1) and then repeat doses of GSK1120212 for (Day 2 through Day 15). The dose regimen of GSK1120212 were continuous dosing. A second single dose of GSK2118436 was administered on Day 15 concomitantly with GSK1120212. Day 16 through Day 28 was a washout period, during which no study medication was administered. Starting on Day 29, subjects who elected to continue participation in the study were doses with GSK2118436. The dose of GSK2118436 after Day 29 might be altered based on emerging data from the first-time-in human study BRF112680. The dose might be increased to a dose level that has been completed and determined to be less than or equal to the maximum tolerated dose in that study. Part B of the study enrolled cohorts in escalating doses to identify a set of allowable doses to be expanded in Part C. Subjects were enrolled in a 3+3 cohort design, with provisional dose levels of both drugs. The decision regarding escalation to the next dose levels of GSK1120212 and GSK2118436 was further guided by a Bayesian logistic regression model. The first cohort started at low doses for both drugs. Doses up to 300 mg/day for GSK2118436 and up to 3 mg QD for GSK1120212 were studied. The starting dose might be lowered based on emerging data from other studies and from Part A. Expansion cohorts enrolled in Part C at dose levels of GSK2118436 and GSK1120212 as defined in Part B. One of the selected doses might include GSK2118436 administered as monotherapy at a tolerable dose (less than or equal to the maximum tolerated dose) determined in BRF112680. Part C was a randomized open-label Phase II portion of the study, and consisted of expansion cohorts investigating 2 to 3 dose levels of GSK2118436 and GSK1120212 dosing in combination, and GSK2118436 administered as monotherapy. Subjects were assigned to treatment arms in a randomized fashion to compare tolerability and safety. Population PK parameters, clinical activity, durability of response and safety of GSK2118436 and GSK1120212 dosed orally in combination and GSK2118436 as monotherapy were evaluated. Part D consisted of evaluation of the pharmacokinetics of GSK2118436 HPMC capsules administered as monotherapy and in combination with GSK1120212. Pharmacokinetics of GSK2118436 was assessed following a single dose on Day 1 and after repeat dosing (Day 21) and compared between combination and monotherapy. The pharmacokinetics of GSK1120212 was also be assessed. Safety, tolerability and clinical activity were evaluated in 4 dosing cohorts. These cohorts might be expanded for additional safety data. Subjects were randomized to different cohorts.
Interventions
DRUGGSK2118436
GSK2118436 is a potent and selective inhibitor of BRAF kinase activity with a mode of action consistent with adenosine triphosphate-competitive inhibition.
DRUGGSK1120212
GSK1120212 is a potent and highly selective inhibitor of MEK1/2 activation and kinase activity.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Capable of given written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Male or female age 18 years or greater; able to swallow and retain oral medication. * BRAF mutation positive melanoma or colorectal cancer; other BRAF mutation positive tumor types may be considered. * Measurable disease according to RECIST version 1.1. * Eastern Cooperative Oncology Group Performance Status of 0 or 1 for Parts A and B. Subjects with Eastern Cooperative Oncology Group Performance Status of 2 or less may be entered into Part C with approval of medical monitor. * Agree to contraception requirements. * Calcium phosphorus product less than 4.0mmol2/L2. * Adequate organ system function. Key
Exclusion criteria
* Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy). * Part A and Part B: Prior exposure to BRAF or MEK inhibitors unless approved by the GSK Medical Monitor. * Part C: Prior exposure to BRAF or MEK inhibitors. Prior anti-cancer therapy in the metastatic setting, with the exception of up to one regimen of chemotherapy and/or interleukin-2 (IL-2). * Part D: Prior exposure to BRAF inhibitors. A washout period of 6 weeks is required for ipilimumab. * Received an investigational anti-cancer drug within 4 weeks or 5 half-lives (whichever is shorter) of study drug administration--- at least 14 days must have passed between the last dose of prior investigational anti-cancer drug and the first dose of study drug. * Current use of a prohibited medication or requires any of these medications during treatment with study drug. * Current use of therapeutic warfarin. * Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks. Limited radiotherapy within the last 2 weeks. * Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks. * Unresolved toxicity greater than National Cancer Institute-Common Terminology Criteria for Adverse Events version 4 Grade 1 from previous anti-cancer therapy except alopecia. * History of retinal vein occlusion, central serous retinopathy or glaucoma. * Predisposing factors to retinal vein occlusion including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy. * Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein occlusion or central serous retinopathy. * Intraocular pressure greater than 21mm Hg as measured by tonography. * Glaucoma diagnosed within one month prior to study Day 1. * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism or excretion of drugs. * Known human immunodeficiency virus, Hepatitis B or Hepatitis C infection. * Primary malignancy of the central nervous system. * Untreated or symptomatic brain metastasis, leptomeningeal disease or spinal cord compression. Subjects who are on a stable dose of corticosteroids for more than 1 month or off corticosteroids for 2 weeks can be enrolled with approval of medical monitor. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs. * Subjects with brain metastases are excluded, unless a. All known lesions must be previously treated with surgery or stereotactic radiosurgery, and- b. Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for ≥90 days prior to first dose on study (must be documented with two consecutive MRI or CT scans using contrast), and c. Asymptomatic with no corticosteroids requirement for ≥ 30 days prior to first dose on study, and d. No enzyme-inducing anticonvulsants for ≥ 30 days prior to first dose on study. * History of alcohol or drug abuse within 6 months prior to screening. * Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol. * QTc interval greater than or equal to 480msecs. * History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks. * Class II, III, or IV heart failure as defined by the New York Heart Association functional classification system. * Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered on study with approval from the medical monitor. * Treatment refractory hypertension defined as a blood pressure of systolic\> 140 mmHg and/or diastolic \> 90 mm Hg which cannot be controlled by anti-hypertensive therapy * Patients with intra-cardiac defibrillators or permanent pacemakers. * Cardiac metastases * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs or excipients. * Pregnant or lactating female. * Unwillingness or inability to follow the procedures required in the protocol. * Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity. * Subjects with known glucose 6 phosphate dehydrogenase deficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | Blood pressure were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to G3 or G4 occurred.lood pressure measurement included systolic blood pressure (BP, milimeter of mercury \[mmHg\]) and diastolic BP (DBP). Worst case change from Baseline was calculated as the post-Baseline value minus the Baseline value. Heart Rate is the measure of heartbeats per minute (bpm). Changes in heart rate, either decrease to \<60 bpm, change to normal or no change, or increase to \>100 bpm are presented |
| Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From Baseline (Day 1) until Follow-up visit (up to approximately 8 years) | An AE is defined as 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 defined as 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. |
| Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | From Baseline (Day 1) until Follow-up visit (up to approximately 8 years) | Clinical Chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis. |
| Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | From Baseline (Day 1) until Follow-up visit (up to approximately 8 years) | For Clinical Chemistry parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis. |
| Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | From Baseline (Day 1) until Follow-up visit (up to approximately 8 years) | Hematology parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis. |
| Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | From Baseline (Day 1) until Follow-up visit (up to approximately 8 years) | For Hematology parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis. |
| Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | From Baseline (Day 1) until Follow-up visit (up to approximately 8 years) | Blood pressure and heart rate were summarized according to NCI CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to G3 or G4 occurred. Blood pressure measurement included systolic blood pressure (SBP, millimeters of mercury \[mmHg\]) and diastolic BP (DBP). Heart rate is the measure of heart beats per minute (bpm). Changes in heart rate, either decrease to \<60 bpm, change to normal or no change, or increase to \>100 bpm are presented. |
| Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 7 years) | Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters \[mm\] in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing responses were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by an investigator as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. |
| Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 19 months) | Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing responses were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by BICR as per RECIST, version 1.1. |
| Part C (Crossover): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 7 years) | Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing responses were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by an investigator as per RECIST, version 1.1. |
| Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Investigator | From the date of randomization to the earliest date of disease progression (PD) or death due to any cause (up to approximately 7 years) | PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not had a documented date of events, PFS and survival were censored at the date of the last adequate assessment. |
| Part C (Crossover): Progression-free Survival (PFS) as Assessed by the Investigator | From the first dose of study medication to the earliest date of disease progression (PD) or death due to any cause (up to approximately 7 years) | PFS is defined as the interval between the first dose of study medication and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. Participants received anti-cancer therapy prior to the date of documented events, and censored at the last adequate assessment, prior to the initiation of therapy. If the participant did not have a documented date of events, PFS and survival were censored at the date of the last adequate assessment. |
| Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Blinded Independent Central Review (BICR) | From the date of randomization to the earliest date of disease progression (PD) or death due to any cause (up to approximately 19 months) | PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the BICR according to RECIST, version 1.1. 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 mm. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not had a documented date of events, PFS and survival were censored at the date of the last adequate assessment |
| Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | First documented evidence of PR or CR until the date of the first documented sign of disease progression or the date of death due to any cause (up to approximately 19 months) | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) 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 \[e.g., percent change from Baseline\]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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 mm. |
| Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | An AE is defined as 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. |
| Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | Clinical Chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis. |
| Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | For Clinical Chemistry parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis. |
| Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | Hematology parameters were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis. |
| Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | For Hematology parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis. |
| Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | Blood pressure were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to G3 or G4 occurred.lood pressure measurement included systolic blood pressure (BP, milimeter of mercury \[mmHg\]) and diastolic BP (DBP). Worst case change from Baseline was calculated as the post-Baseline value minus the Baseline value. Heart Rate is the measure of heart beats per minute (bpm). Changes in heart rate, either decrease to \<60 bpm, change to normal or no change, or increase to \>100 bpm are presented. |
| Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 and Day 21 | The PK parameter Cmax was assessed. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (24 hour on Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Cmax data are reported as geometric least squares means. |
| Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 and Day 21 | tmax is defined as the time of occurenceof Cmax. Blood samples for PK analysis of dabrafenib were obtained at Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours (24 hour on Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. |
| Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | Day 1 and Day 21 | The PK parameters were determined for area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration AUC (0-tau) and from time zero (pre-dose) extrapolated to infinite time AUC (0-inf). Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (24 hour only on Day 1) post-dose administration. |
| Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | An AE is defined as 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 for possible drug-induced liver injury. |
| Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | Clinical Chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis. |
| Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | For Clinical Chemistry parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis. |
| Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | Hematology parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis. |
| Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | From Baseline (Day 1) until Follow-up visit (up to approximately 7 years) | For Hematology parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis. |
| Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | Day 15 | Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. Cmax data are reported as geometric least squares means. |
| Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | Day 15 | Blood samples for PK analysis of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. AUC is defined as the area under the dabrafenib concentration-time curve as a measure of drug exposure. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC (0-t) is defined as area under the concentration-time curve from time zero (pre-dose) to the last time of quantifiable concentration. Date are reported as geometric least square means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | Day 15 and Day 21 | Area under the concentration-time curve from time zero (predose) until the last time of quantifiable concentration (AUC \[0-tau\]) was assessed. Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration. |
| Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | Day 15 and Day 21 | Pre-dose (trough) concentration at the end of the dosing interval (Ctau) and maximum plasma concentration (Cmax) were assessed for plasma dabrafenib (DAB) following repeat dosing of DAB administered in combination with trametinib (T). The trough concentration is defined as the plasma level of a pharmaceutical product measured just before the next dose. Blood samples for PK analysis of the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration. |
| Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | Day 15 and Day 21 | The tmax is defined as the time of occurenceof Cmax. Tha tmax was assessed for plasma dabrafenib (DAB) following repeat dosing of dabrafenib 75 and 150 mg BID administered in combination with trametinib. Blood samples for PK analysis of the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration. |
| Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 15 and Day 21 | AUC (0-tau) is defined as area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration. AUC (0-tau) was assessed for plasma trametinib following repeat dosing of trametinib in combination with dabrafenib. Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration. |
| Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Day 15 and Day 21 | Pre-dose (trough) concentration at the end of the dosing interval (Ctau) and maximum plasma concentration (Cmax) were assessed for plasma trametinib following repeat dosing of trametinib in combination with dabrafenib. Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 15 pre-dose or Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration. |
| Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 15 and Day 21 | The tmax is defined as the time of occurrence of Cmax. The PK parameter for tmax was assessed for plasma trametinib following repeat dosing of trametinib in combination with dabrafenib. Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 15 pre-dose or Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration. |
| Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 8 years) | Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 milimeter \[mm\] in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing response were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by an investigator as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. BRAFi-naïve participants were those with BRAF-mutation-positive melanoma who had not received prior therapy with a BRAF inhibitor. |
| Part B: Duration of Response as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | First documented evidence of PR or CR until the earlier of date of disease progression or date of death due to any cause (up to approximately 8 years) | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) 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 \[e.g., percent change from Baseline\]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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 mm. BRAFi-naïve participants were those with BRAF-mutation-positive melanoma who had not received prior therapy with a BRAF inhibitor. |
| Part B: Progression-free Survival (PFS) as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | From the date of first dose to the earliest date of disease progression (PD) or death due to any cause (up to approximately 8 years) | PFS is defined as the interval between the first dose of study medication and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. BRAFi-naïve were the participants with BRAF-mutation positive melanoma who had not received prior therapy with a BRAF-inhibitor.. |
| Part B: Overall Survival (OS) in BRAFi Naïve Melanoma Participants | From the date of first dose until date of death due to any cause (up to approximately 8 years) | OS is defined as the interval of time between the first dose of study medication until the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact. |
| Part B: Pre- and Post-dose H-scores for Individual Participants | Screening and at disease progression (up to approximately 8 years) | p-ERK and p-AKT, biomarkers in tumor biopsies, were assessed for participants with BRAF mutant colorectal cancer. The H-score, which is a composite score that comprises intensity and percentage of staining, is a method of assessing the amount of protein or phospho-protein present in a biopsy sample. The score is obtained by the formula: (3 \* percentage of strongly staining nuclei) + (2 \* percentage of moderately staining nuclei) + (percentage of weakly staining nuclei). The H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein. |
| Part C (Randomized): Overall Survival (OS) | From the date of randomization until date of death due to any cause (up to approximately 7 years) | OS is defined as the interval of time between the date of randomization until the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact. When calculating overall survival, deaths following crossover were included. |
| Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 56 | Plasma concentrations of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were assesed following daily dose of dabrafenib and trametinib. |
| Part C: Plasma Concentrations of Trametinib | Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 56 | Plasma concentrations of trametinib was assessed following daily dose of dabrafenib and trametinib. |
| Part C: Oral Clearance (CL/F) of Dabrafenib and Trametinib | Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48 | Oral clearance (CL/F) of dabrafenib and trametinib were assessed using a population approach. Oral clearance (CL/F) is defined as the apparent volume of plasma in the vascular compartment cleared of drug per unit time by the processes of metabolism and excretion. For dabrafenib, population CL/F is defined as inducible and non-inducible CL/F. As dabrafenib induces its own metabolism, total oral clearance at steady state includes a non-induced (Day 1) component and an induced component, as estimated by a population PK model. |
| Part C: Oral Volume of Distribution (V/F) of Dabrafenib and Trametinib | Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48 | Oral volume of distribution (V/F) of dabrafenib and trametinib were assessed using a population approach. Oral volume of distribution (V/F) is defined as the apparent volume of distribution in the central compartment. |
| Part D: Cmax of Dabrafenib Metabolites | Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose | The maximum concentration (Cmax) of dabrafenib metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) after single and repeat doses of DAB alone and in combination with trametinib was measured at Day 1 and Day 21. |
| Part D: Tmax of Dabrafenib Metabolites | Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose | The time to Cmax (tmax) of DAB metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) after single and repeat doses of DAB alone and in combination with trametinib was measuered at Day 1 and Day 21. |
| Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose | Area under the concentration-time curve (AUC) from pre-dose to dosing interval (AUC\[0-tau\]), from pre-dose to the last time of quantifable concentration (AUC\[0-tau\]), and from pre-dose extrapolated to infinity (AUC\[0-inf\]) of DAB metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) after single and repeat doses of DAB alone and in combination with trametinib was measured at Day 1 and Day 21. |
| Part D: Cmax Assessment of Trametinib | Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose | Cmax of trametinib after single and repeat dose in combination with DAB was observed at Day 1 and Day 21. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.Participants receiving DAB 75 mg to DAB 75 mg + Trametinib 2 mg and those receiving DAB 150 mg to DAB 150 mg + Trametinib 2 mg did not receive Trametinib until Day 29; therefore, Cmax was not analyzed in these participants at Days 1 and 21. |
| Part D: Tmax Assessment of Trametinib | Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose | The tmax of trametinib after single and repeat dose in combination with dabrafenib (DAB) was observed at Day 1 and Day 21. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.Participants receiving DAB 75 mg to DAB 75 mg + Trametinib 2 mg and those receiving DAB 150 mg to DAB 150 mg + Trametinib 2 mg did not receive Trametinib until Day 29; therefore, tmax was not analyzed in these participants at Days 1 and 21. |
| Part D: Area Under the Concentration-time Curve Assessment of Trametinib | Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose | AUC(0-tau) after single and repeat dose of teametinib alone and in combination with dabrafenib was observed at Day 1 and Day 21. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.Participants receiving DAB 75 mg to DAB 75 mg + Trametinib 2 mg and those receiving DAB 150 mg to DAB 150 mg + Trametinib 2 mg did not receive Trametinib until Day 29; therefore, AUC(0-tau) was not analyzed in these participants at Days 1 and 21. |
| Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | From the date of first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 7 years) | Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 milimeter \[mm\] in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). To be assigned a status of PR or CR, a confirmatory disease assessment should be performed no less than 28 days after the criteria for response are first met. Response was evaluated by an investigator as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. |
| Part D: Duration of Response as Assessed by the Investigator | First documented evidence of PR or CR until the earlier of date of disease progression or date of death due to any cause (up to approximately 7 years) | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) 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 \[e.g., percent change from Baseline\]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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 mm. |
| Part D: Progression-free Survival (PFS) as Assessed by the Investigator | From the date of randomization to the earliest date of disease progression (PD) or death due to any cause (up to approximately 7 years) | PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. |
| Part D: Overall Survival (OS) | From the date of first dose until date of death due to any cause (up to approximately 7 years) | OS is defined as the interval of time between the date of randomization until the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact. |
| Part A: Steady State Concentration of Trametinib With Concomitant Administration of Dabrafenib | Day 15 and Day 16 | The steady state plasma concentration (Css) of trametinib with concomitant dabrafenib administration was assessed at Day 15 and Day 16. At steady state the amount of drug administered (in a given time period) is equal to the amount of drug eliminated. |
Countries
Australia, United States
Participant flow
Recruitment details
This study was conducted in 16 sites: Australia (2) and USA (14)
Pre-assignment details
The study was comprised of Parts A, B, and D, which constitute the Phase I part of the study, and Part C, which constitutes the randomized Phase II part of the study. Participants did not enroll in all parts of the study sequentially. Each part of the study was comprised of a separate population of participants.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg Participants received a single dose of dabrafenib 75 mg gelatin capsules with repeat dose trametinib (Day 15). | 8 |
| Part B: Dabrafenib 75 mg + Trametinib 1 mg Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 75 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available pharmacokinetic (PK), safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on dose-limiting toxicities (DLTs) occurring during the first 3 weeks of treatment. | 6 |
| Part B: Dabrafenib 150 mg + Trametinib 1 mg Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors and participants who had salivary ductal cancer received dabrafenib 150 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment. | 23 |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 150 mg gelatin capsules BID and trametinib 1.5 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment. | 27 |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg Melanoma BRAF-positive participants who received prior treatment with BRAF inhibitors and participants who had colorectal cancer and BRAFi naïve melanoma received dabrafenib 150 mg gelatin capsules BID and trametinib 2 mg tablets QD as continuous daily dosing. Dose escalation did not proceed beyond these doses of dabrafenib and trametinib. | 94 |
| Part C: Dabrafenib 150 mg Participants received dabrafenib 150 mg gelatin capsules BID. | 54 |
| Part C: Dabrafenib 150 mg + Trametinib 1 mg Participants received dabrafenib 150 mg gelatin capsules BID and trametinib 1 mg tablets QD. | 54 |
| Part C: Dabrafenib 150 mg + Trametinib 2 mg Participants received dabrafenib 150 mg gelatin capsules BID and trametinib 2 mg tablets QD. | 54 |
| Part D: Dabrafenib (DAB) 75 mg to DAB 75 mg + Trametinib 2 mg Participants received dabrefinib 75 mg HPMC capsules BID. These participants, after completion of serial PK collection in the first treatment period, were allowed to continue with dabrafenib 75 mg BID and trametinib 2 mg tablets QD as combination dosing starting on Day 29. | 12 |
| Part D: Dabrafenib 150 mg to DAB 150 mg + Trametinib 2 mg Participants received dabrefinib 150 mg HPMC capsules BID. These participants, after completion of serial PK collection in the first treatment period, were allowed to continue with dabrafenib 150 mg BID and trametinib 2 mg tablets QD as combination dosing starting on Day 29. | 16 |
| Part D: Dabrafenib 75 mg + Trametinib 2 mg Participants received dabrefinib 75 mg HPMC capsules BID and trametinib 2 mg tablets QD. | 43 |
| Part D: Dabrafenib 150 mg + Trametinib 2 mg Participants received dabrefinib 150 mg HPMC capsules BID and trametinib 2 mg tablets QD. | 39 |
| Total | 430 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A (Drug-Drug Interaction) | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A (Drug-Drug Interaction) | Physician Decision | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A (Drug-Drug Interaction) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Dose Escalation and Expansion) | Death | 0 | 4 | 18 | 21 | 68 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Dose Escalation and Expansion) | Lost to Follow-up | 0 | 1 | 0 | 1 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Dose Escalation and Expansion) | Physician Decision | 0 | 0 | 2 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Dose Escalation and Expansion) | Study closed/terminated | 0 | 0 | 3 | 2 | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Dose Escalation and Expansion) | Withdrawal by Subject | 0 | 1 | 0 | 3 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Crossover Phase [CP]) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 37 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Crossover Phase [CP]) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Crossover Phase [CP]) | Study closed/terminated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Crossover Phase [CP]) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Randomized Phase) | Death | 0 | 0 | 0 | 0 | 0 | 44 | 34 | 39 | 0 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Randomized Phase) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Randomized Phase) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Randomized Phase) | Study closed/terminated | 0 | 0 | 0 | 0 | 0 | 6 | 9 | 11 | 0 | 0 | 0 | 0 | 0 |
| Part C (Phase II: Randomized Phase) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 3 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part D (HPMC Capsules) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 10 | 12 | 28 | 26 |
| Part D (HPMC Capsules) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 |
| Part D (HPMC Capsules) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Part D (HPMC Capsules) | Study closed/terminated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 10 | 9 |
| Part D (HPMC Capsules) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Dabrafenib 75 mg + Trametinib 1 mg | Part B: Dabrafenib 150 mg + Trametinib 1 mg | Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part C: Dabrafenib 150 mg | Part C: Dabrafenib 150 mg + Trametinib 1 mg | Part C: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Dabrafenib (DAB) 75 mg to DAB 75 mg + Trametinib 2 mg | Part D: Dabrafenib 150 mg to DAB 150 mg + Trametinib 2 mg | Part D: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Dabrafenib 150 mg + Trametinib 2 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.8 Years STANDARD_DEVIATION 16.04 | 48.2 Years STANDARD_DEVIATION 7.28 | 54.2 Years STANDARD_DEVIATION 13.24 | 52.2 Years STANDARD_DEVIATION 12.09 | 52.4 Years STANDARD_DEVIATION 12.99 | 51.8 Years STANDARD_DEVIATION 15.19 | 49.9 Years STANDARD_DEVIATION 14.7 | 55.9 Years STANDARD_DEVIATION 11.85 | 51.8 Years STANDARD_DEVIATION 12.39 | 53.1 Years STANDARD_DEVIATION 17.04 | 52.8 Years STANDARD_DEVIATION 14.57 | 56.7 Years STANDARD_DEVIATION 14.08 | 52.8 Years STANDARD_DEVIATION 13.74 |
| Race/Ethnicity, Customized African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 6 Participants | 22 Participants | 26 Participants | 92 Participants | 52 Participants | 54 Participants | 53 Participants | 12 Participants | 16 Participants | 43 Participants | 39 Participants | 407 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 10 Participants | 12 Participants | 56 Participants | 25 Participants | 24 Participants | 20 Participants | 6 Participants | 8 Participants | 18 Participants | 14 Participants | 197 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 13 Participants | 15 Participants | 38 Participants | 29 Participants | 30 Participants | 34 Participants | 6 Participants | 8 Participants | 25 Participants | 25 Participants | 233 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 8 | 0 / 6 | 1 / 23 | 6 / 27 | 12 / 94 | 1 / 53 | 4 / 54 | 7 / 55 | 7 / 45 | 1 / 15 | 4 / 15 | 7 / 41 | 2 / 39 |
| other Total, other adverse events | 8 / 8 | 6 / 6 | 23 / 23 | 27 / 27 | 91 / 94 | 53 / 53 | 53 / 54 | 55 / 55 | 44 / 45 | 15 / 15 | 15 / 15 | 41 / 41 | 37 / 39 |
| serious Total, serious adverse events | 5 / 8 | 1 / 6 | 15 / 23 | 14 / 27 | 55 / 94 | 15 / 53 | 24 / 54 | 39 / 55 | 24 / 45 | 8 / 15 | 11 / 15 | 29 / 41 | 30 / 39 |
Outcome results
Primary
Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites
Blood samples for PK analysis of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. AUC is defined as the area under the dabrafenib concentration-time curve as a measure of drug exposure. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC (0-t) is defined as area under the concentration-time curve from time zero (pre-dose) to the last time of quantifiable concentration. Date are reported as geometric least square means.
Time frame: Day 15
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2118436 AUC (0-t) | 2734 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2118436 AUC (0-inf) | 3128 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2285403 AUC (0-t) | 2232 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2285403 AUC (0-inf) | 2819 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2298683 AUC (0-t) | 12761 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2167542 AUC (0-t) | 270 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2298683 AUC (0-t) | 13053 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2118436 AUC (0-t) | 2751 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2285403 AUC (0-inf) | 2497 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2118436 AUC (0-inf) | 2949 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2167542 AUC (0-t) | 276 ng*hour/mL (ng*hr/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites | GSK2285403 AUC (0-t) | 2287 ng*hour/mL (ng*hr/mL) |
90% CI: [0.85, 1.19]
90% CI: [0.82, 1.08]
90% CI: [0.84, 1.25]
90% CI: [0.81, 1.03]
90% CI: [0.81, 1.29]
90% CI: [0.76, 1.37]
Primary
Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib
Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. Cmax data are reported as geometric least squares means.
Time frame: Day 15
Population: Pharmacokinetic (PK) Population: all participants who received at least one dose of either dabrafenib or trametinib and for whom a PK sample was obtained and analyzed
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2118436 | 509 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2285403 | 259 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2298683 | 724 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2167542 | 8.37 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2167542 | 8.16 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2118436 | 524 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2298683 | 747 Nanograms per milliliter (ng/mL) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib | GSK2285403 | 255 Nanograms per milliliter (ng/mL) |
90% CI: [0.79, 1.34]
90% CI: [0.78, 1.25]
90% CI: [0.84, 1.27]
90% CI: [0.66, 1.45]
Primary
Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as 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 defined as 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 Baseline (Day 1) until Follow-up visit (up to approximately 8 years)
Population: All Treated Participants (ATP) Population: all participants who received at least one dose of either dabrafenib or trametinib
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 23 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 15 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 27 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 14 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 55 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 93 Participants |
Primary
Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure
Blood pressure and heart rate were summarized according to NCI CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to G3 or G4 occurred. Blood pressure measurement included systolic blood pressure (SBP, millimeters of mercury \[mmHg\]) and diastolic BP (DBP). Heart rate is the measure of heart beats per minute (bpm). Changes in heart rate, either decrease to \<60 bpm, change to normal or no change, or increase to \>100 bpm are presented.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 8 years)
Population: ATP Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | SBP, Increase to G3 or G4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 3 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | DBP, Increase to G3 or G4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 7 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | SBP, Increase to G3 or G4 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | DBP, Increase to G3 or G4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 14 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 15 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | SBP, Increase to G3 or G4 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | DBP, Increase to G3 or G4 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | SBP, Increase to G3 or G4 | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 37 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 15 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 26 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | DBP, Increase to G3 or G4 | 4 Participants |
Primary
Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range
For Clinical Chemistry parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 8 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 7 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Increase to High | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Increase to High | 9 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Decrease to Low | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Decrease to Low | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 16 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Decrease to Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Decrease to Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Increase to High | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Decrease to Low | 19 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine clearance | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Decrease to Low | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate dehydrogenase | Increase to High | 35 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Decrease to Low | 30 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total protein | Increase to High | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Indirect Bilirubin | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 17 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 16 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Trponin T | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 16 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 39 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 25 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 30 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
Primary
Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline
Clinical Chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 8 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Blood pH | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 13 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 5 Participants |
Primary
Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range
For Hematology parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 8 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 9 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 9 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 21 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 30 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 13 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 24 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 25 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 28 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 21 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 13 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 3 Participants |
Primary
Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline
Hematology parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 8 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 7 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 19 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 3 | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell Count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
Primary
Part C (Crossover): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator
Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing responses were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by an investigator as per RECIST, version 1.1.
Time frame: From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 7 years)
Population: Crossover Population: participants who were randomized to and received at least one dose of dabrafenib monotherapy, and who elected to crossover to combination therapy following disease progression while on monotherapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Crossover): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | CR | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Crossover): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | PR | 5 Participants |
95% CI: [5.1, 26.8]
Primary
Part C (Crossover): Progression-free Survival (PFS) as Assessed by the Investigator
PFS is defined as the interval between the first dose of study medication and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. Participants received anti-cancer therapy prior to the date of documented events, and censored at the last adequate assessment, prior to the initiation of therapy. If the participant did not have a documented date of events, PFS and survival were censored at the date of the last adequate assessment.
Time frame: From the first dose of study medication to the earliest date of disease progression (PD) or death due to any cause (up to approximately 7 years)
Population: Crossover Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Crossover): Progression-free Survival (PFS) as Assessed by the Investigator | 3.6 Months |
Primary
Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR)
Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) 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 \[e.g., percent change from Baseline\]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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 mm.
Time frame: First documented evidence of PR or CR until the date of the first documented sign of disease progression or the date of death due to any cause (up to approximately 19 months)
Population: ITT Population. Only those participants who had a CR or PR were analyzed for duration of response.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | Investigator assessed | 5.6 Months |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | BICR assessed | 7.6 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | Investigator assessed | 11.1 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | BICR assessed | 9.5 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | Investigator assessed | 10.5 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Duration of Response as Assessed by the Investigator and Blinded Independent Central Review (BICR) | BICR assessed | NA Months |
Primary
Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as 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 Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: ATP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 53 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 15 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 53 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 24 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 55 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 39 Participants |
Primary
Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator
Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters \[mm\] in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing responses were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by an investigator as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
Time frame: From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 7 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not treatment was administered
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | CR | 2 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | PR | 27 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | CR | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | PR | 21 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | CR | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response as Assessed by the Investigator | PR | 31 Participants |
Comparison: Difference in response rate Arm2 - Arm195% CI: [-23.1, 15.9]
Comparison: Difference in response rate Arm3 - Arm195% CI: [2.5, 40.7]
Primary
Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing responses were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by BICR as per RECIST, version 1.1.
Time frame: From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 19 months)
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | CR | 4 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PR | 21 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | CR | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PR | 18 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | CR | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With BRAF Mutant Metastatic Melanoma With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PR | 26 Participants |
Comparison: Difference in response rate Arm2- Arm195% CI: [-24.9, 14.1]
Comparison: Difference in response rate Arm3 - Arm195% CI: [-4.9, 33.7]
Primary
Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure
Blood pressure were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to G3 or G4 occurred.lood pressure measurement included systolic blood pressure (BP, milimeter of mercury \[mmHg\]) and diastolic BP (DBP). Worst case change from Baseline was calculated as the post-Baseline value minus the Baseline value. Heart Rate is the measure of heart beats per minute (bpm). Changes in heart rate, either decrease to \<60 bpm, change to normal or no change, or increase to \>100 bpm are presented.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: ATP Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 34 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 9 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , G3 or G4 | 5 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), G3 or G4 | 4 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , G3 or G4 | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), G3 or G4 | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 30 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 16 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 18 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 28 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , G3 or G4 | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), G3 or G4 | 4 Participants |
Primary
Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range
For Clinical Chemistry parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: ATP Population. Only those participants who were available at the indicated time points were analyzed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 7 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 11 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 8 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease to Low | 7 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 7 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids, Cholesterol | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids, Cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids, Cholesterol | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids, Cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids, Cholesterol | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids, Cholesterol | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease to Low | 16 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids, Cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids, Cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 24 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease to Low | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 14 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 23 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 24 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease to Low | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 14 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 16 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease to Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease to Low | 9 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids, Cholesterol | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids, Cholesterol | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease to Low | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 20 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 32 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids, Cholesterol | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease to Low | 24 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids, Cholesterol | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease to Low | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease to Low | 19 Participants |
Primary
Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline
Clinical Chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
Primary
Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range
For Hematology parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 15 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 3 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 11 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 6 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 8 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 17 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 11 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 14 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 6 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 16 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 22 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 20 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 23 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 9 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 25 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 9 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 27 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 14 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 5 Participants |
Primary
Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline
Hematology parameters were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet Count | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
Primary
Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Blinded Independent Central Review (BICR)
PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the BICR according to RECIST, version 1.1. 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 mm. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not had a documented date of events, PFS and survival were censored at the date of the last adequate assessment
Time frame: From the date of randomization to the earliest date of disease progression (PD) or death due to any cause (up to approximately 19 months)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Blinded Independent Central Review (BICR) | 7.3 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Blinded Independent Central Review (BICR) | 8.3 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Blinded Independent Central Review (BICR) | 9.2 Months |
p-value: 0.166795% CI: [0.45, 1.18]Log Rank
p-value: 0.011995% CI: [0.32, 0.9]Log Rank
Primary
Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Investigator
PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not had a documented date of events, PFS and survival were censored at the date of the last adequate assessment.
Time frame: From the date of randomization to the earliest date of disease progression (PD) or death due to any cause (up to approximately 7 years)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Investigator | 5.8 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Investigator | 9.2 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Progression-free Survival (PFS) as Assessed by the Investigator | 9.4 Months |
p-value: 0.004895% CI: [0.38, 0.87]Log Rank
p-value: <0.000195% CI: [0.29, 0.68]Log Rank
Primary
Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib
The PK parameters were determined for area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration AUC (0-tau) and from time zero (pre-dose) extrapolated to infinite time AUC (0-inf). Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (24 hour only on Day 1) post-dose administration.
Time frame: Day 1 and Day 21
Population: PK Population. Only participants available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 1 | 3593 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-inf), Day 1 | 3982 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 21 | 3020 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 1 | 6507 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-inf), Day 1 | 7291 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 21 | 4663 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 21 | 3434 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 1 | 4618 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-inf), Day 1 | 5321 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 1 | 7331 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-inf), Day 1 | 8152 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib | AUC (0-tau), Day 21 | 5886 ng*hr/mL |
90% CI: [0.89, 1.69]
90% CI: [0.84, 1.44]
Primary
Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib
The PK parameter Cmax was assessed. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (24 hour on Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Cmax data are reported as geometric least squares means.
Time frame: Day 1 and Day 21
Population: PK Population: all participants who received at least one dose of either dabrafenib or trametinib and for whom a PK sample was obtained and analyzed
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 1117 ng/mL |
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1050 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1746 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 1669 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 1227 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1217 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 2289 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Maximum Plasma Concentration (Cmax) of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 2052 ng/mL |
90% CI: [1.1, 2.08]
Primary
Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib
tmax is defined as the time of occurenceof Cmax. Blood samples for PK analysis of dabrafenib were obtained at Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours (24 hour on Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.
Time frame: Day 1 and Day 21
Population: PK Population. Only participants available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 2.00 Hours |
| Part A: Dabrafenib 75 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1.50 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1.55 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1.75 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 1 | 1.50 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib | Day 21 | 1.50 Hours |
Primary
Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as 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 for possible drug-induced liver injury.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: ATP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 15 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 11 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 15 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 41 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 29 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 38 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 30 Participants |
Primary
Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure
Blood pressure were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to G3 or G4 occurred.lood pressure measurement included systolic blood pressure (BP, milimeter of mercury \[mmHg\]) and diastolic BP (DBP). Worst case change from Baseline was calculated as the post-Baseline value minus the Baseline value. Heart Rate is the measure of heartbeats per minute (bpm). Changes in heart rate, either decrease to \<60 bpm, change to normal or no change, or increase to \>100 bpm are presented
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: ATP Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), increase to G3 or G4 | 4 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , increase to G3 or G4 | 3 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 5 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 9 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , increase to G3 or G4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), increase to G3 or G4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 18 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), increase to G3 or G4 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , increase to G3 or G4 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Diastolic BP (mmHg), increase to G3 or G4 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Increase to >100 bpm | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Decrease to <60 bpm | 14 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Heart rate, Change to normal or no change | 17 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Indicated Worst-case Change From Baseline in Heart Rate and Blood Pressure | Systolic BP (mmHg) , increase to G3 or G4 | 6 Participants |
Primary
Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range
For Clinical Chemistry parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease Low | 5 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease Low | 5 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease Low | 7 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 7 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease Low | 3 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease Low | 9 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease Low | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease Low | 5 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease Low | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 7 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease Low | 7 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Decrease Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease Low | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease Low | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease Low | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 20 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease Low | 18 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease Low | 17 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease Low | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Decrease Low | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Increase to High | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Increase to High | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Increase to High | 9 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Increase to High | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Decrease Low | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Increase to High | 13 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Lactate Dehydrogenase | Increase to High | 20 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Chloride | Decrease Low | 25 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | High Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Urea/BUN | Decrease Low | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Decrease Low | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin T | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | C-Reactive protein | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Low Density Lipids cholesterol | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatine Kinase MB mass | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Direct Bilirubin | Decrease Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Creatinine Clearance | Increase to High | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Total Protein | Decrease Low | 15 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Troponin I | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Change From Baseline With Respect to Normal Range | Carbon dioxide content/Bicarbonate | Decrease Low | 8 Participants |
Primary
Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline
Clinical Chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hyperglycemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Albumin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Gamma Glutamyl Transferase | Increase to Grade 3 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatinine | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alkaline Phosphatase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hyponatremia) | Increase to Grade 3 | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Creatine Kinase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Aspartate Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Alanine Amino Transferase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypomagnesemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Sodium (Hypernatremia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hypokalemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Potassium (Hyperkalemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypercalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Uric acid | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Cholesterol | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Lipase | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Total Bilirubin | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Phosphorus inorganic | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Amylase | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Triglycerides | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Glucose (Hypoglycemia) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Calcium (Hypocalcemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Chemistry Toxicity Grade Change From Baseline | Magnesium (Hypermagnesemia) | Increase to Grade 4 | 0 Participants |
Primary
Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range
For Hematology parameters that were not graded according to NCI CTCAE criteria, changes above (High) and below (Low) the normal range were evaluated. Participants with missing Baseline were assumed to be within normal range. Participants were counted twice if the subject Decreased to Low and Increase to High during the post-baseline period. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 7 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 4 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 5 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 3 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 6 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Decrease to Low | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 2 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Increase to High | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 19 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 10 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 12 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 17 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 26 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Increase to High | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin concentration | Decrease to Low | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Decrease to Low | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Increase to High | 13 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Hematocrit | Decrease to Low | 18 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Decrease to Low | 17 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Erythrocyte Sedimentation Rate | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Basophils | Decrease to Low | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Red Blood Cell count | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Increase to High | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Decrease to Low | 9 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Eosinophils | Decrease to Low | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Volume | Increase to High | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Increase to High | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Mean Corpuscle Hemoglobin | Decrease to Low | 6 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Reticulocytes | Increase to High | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Change From Baseline With Respect to Normal Range | Monocytes | Decrease to Low | 12 Participants |
Primary
Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline
Hematology parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline Grade were assumed to have Baseline Grade of 0. All increases were an increase in grade from Baseline. Only descriptive analysis.
Time frame: From Baseline (Day 1) until Follow-up visit (up to approximately 7 years)
Population: All Treated Participants (ATP) Population. Only participants with lab values at the specified planned time were considered.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 3 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 1 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 3 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 4 | 0 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 3 | 11 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Lymphocytes (Decreased) | Increase to Grade 4 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 3 | 1 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Platelet count | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Anemia) | Increase to Grade 4 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Total Neutrophils | Increase to Grade 3 | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | Hemoglobin (Increased) | Increase to Grade 3 | 0 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With Worst-case Hematology Toxicity Grade Change From Baseline | White Blood Cell count | Increase to Grade 3 | 3 Participants |
Secondary
Part A: Steady State Concentration of Trametinib With Concomitant Administration of Dabrafenib
The steady state plasma concentration (Css) of trametinib with concomitant dabrafenib administration was assessed at Day 15 and Day 16. At steady state the amount of drug administered (in a given time period) is equal to the amount of drug eliminated.
Time frame: Day 15 and Day 16
Population: PK Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part A: Steady State Concentration of Trametinib With Concomitant Administration of Dabrafenib | Day 15 | 9.7 ng/mL |
| Part A: Dabrafenib 75 mg | Part A: Steady State Concentration of Trametinib With Concomitant Administration of Dabrafenib | Day 16 | 10.2 ng/mL |
Secondary
Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib
AUC (0-tau) is defined as area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration. AUC (0-tau) was assessed for plasma trametinib following repeat dosing of trametinib in combination with dabrafenib. Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Time frame: Day 15 and Day 21
Population: PK Population. Only those participants who were available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 169 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 147 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 21 | 169 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 21 | 269 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 217 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 394 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): AUC (0-tau) Assessment of Trametinib in Combination With Dabrafenib | Day 21 | 351 ng*hr/mL |
Secondary
Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib
Pre-dose (trough) concentration at the end of the dosing interval (Ctau) and maximum plasma concentration (Cmax) were assessed for plasma trametinib following repeat dosing of trametinib in combination with dabrafenib. Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 15 pre-dose or Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Time frame: Day 15 and Day 21
Population: PK Population. Only those participants who were available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 15 | 5.56 ng/mL |
| Part A: Dabrafenib 75 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 15 | 10.2 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 15 | 5.05 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 21 | 5.57 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 15 | 8.08 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 21 | 10.2 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 21 | 18.0 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 15 | 11.5 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 15 | 7.62 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 21 | 8.51 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 15 | 22.4 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Cmax, Day 21 | 22.6 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 21 | 10.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Ctau and Cmax Assessments of Trametinib in Combination With Dabrafenib | Ctau, Day 15 | 12.4 ng/mL |
Secondary
Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib
The tmax is defined as the time of occurrence of Cmax. The PK parameter for tmax was assessed for plasma trametinib following repeat dosing of trametinib in combination with dabrafenib. Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 15 pre-dose or Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Time frame: Day 15 and Day 21
Population: PK Population. Only those participants who were available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 15 | 1.52 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B (Analyte=GSK1120212): Tmax Assessment of Trametinib in Combination With Dabrafenib | Day 21 | 2.00 Hours |
Secondary
Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib
Area under the concentration-time curve from time zero (predose) until the last time of quantifiable concentration (AUC \[0-tau\]) was assessed. Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Time frame: Day 15 and Day 21
Population: PK Population. Only those participants who were available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 15 | 2466 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 15 | 2120 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683, Day 15 | 37159 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 15 | 2859 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 21 | 3609 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683 , Day 21 | 47911 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 15 | 2163 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683, Day 15 | 40634 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 21 | 4656 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 15 | 3539 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 15 | 2961 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 21 | 3257 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683, Day 15 | 43727 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 21 | 4528 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 15 | 3136 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 21 | 2989 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 21 | 2995 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683 , Day 21 | 49939 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 15 | 4156 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 15 | 5187 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683 , Day 21 | 59965 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 21 | 3961 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 15 | 3180 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 15 | 4114 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2167542, Day 15 | 3746 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2298683, Day 15 | 68528 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | GSK2285403, Day 21 | 3632 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib | DAB, Day 21 | 5518 ng*hr/mL |
Secondary
Part B: Duration of Response as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma
Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) 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 \[e.g., percent change from Baseline\]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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 mm. BRAFi-naïve participants were those with BRAF-mutation-positive melanoma who had not received prior therapy with a BRAF inhibitor.
Time frame: First documented evidence of PR or CR until the earlier of date of disease progression or date of death due to any cause (up to approximately 8 years)
Population: All Treated Population. Only those participants who had a CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Duration of Response as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 12.4 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Duration of Response as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 8.4 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Duration of Response as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 12.6 Months |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Duration of Response as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 16.9 Months |
Secondary
Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator
Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 milimeter \[mm\] in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). Participants with unknown or missing response were considered as non-responders. To be assigned a status of PR or CR, a confirmatory disease assessment should have been performed no less than 28 days after the criteria for response were first met. Response was evaluated by an investigator as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. BRAFi-naïve participants were those with BRAF-mutation-positive melanoma who had not received prior therapy with a BRAF inhibitor.
Time frame: From the first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 8 years)
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | CR | 0 Participants |
| Part A: Dabrafenib 75 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | PR | 4 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | PR | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | CR | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | CR | 3 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | PR | 8 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | CR | 4 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Number of Participants With BRAFi-naïve Mutant Metastatic Melanoma With the Best Overall Response as Assessed by Investigator | PR | 11 Participants |
Secondary
Part B: Overall Survival (OS) in BRAFi Naïve Melanoma Participants
OS is defined as the interval of time between the first dose of study medication until the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact.
Time frame: From the date of first dose until date of death due to any cause (up to approximately 8 years)
Population: All Treated Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Overall Survival (OS) in BRAFi Naïve Melanoma Participants | 17.4 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Overall Survival (OS) in BRAFi Naïve Melanoma Participants | 23.5 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Overall Survival (OS) in BRAFi Naïve Melanoma Participants | 13.3 Months |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Overall Survival (OS) in BRAFi Naïve Melanoma Participants | 41.5 Months |
Secondary
Part B: Pre- and Post-dose H-scores for Individual Participants
p-ERK and p-AKT, biomarkers in tumor biopsies, were assessed for participants with BRAF mutant colorectal cancer. The H-score, which is a composite score that comprises intensity and percentage of staining, is a method of assessing the amount of protein or phospho-protein present in a biopsy sample. The score is obtained by the formula: (3 \* percentage of strongly staining nuclei) + (2 \* percentage of moderately staining nuclei) + (percentage of weakly staining nuclei). The H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.
Time frame: Screening and at disease progression (up to approximately 8 years)
Population: Biomarker Population: participants with H-score data for pre- and post-biopsy pairs
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 1, pre-dose score | 135 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 1, post-dose score | 109 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 2, pre-dose score | 193 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 2, post-dose score | 138 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 3, pre-dose score | 148 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 3, post-dose score | 65 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 4, pre-dose score | 80 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 4, post-dose score | 20 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 5, pre-dose score | 130 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 5, post-dose score | 99 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 6, pre-dose score | 68 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 6, post-dose score | 7 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 7, pre-dose score | 128 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 7, post-dose score | 81 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 8, pre-dose score | 196 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 8, post-dose score | 75 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 9, pre-dose score | 164 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 9, post-dose score | 109 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 10, pre-dose score | 239 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-ERK: Participant 10, post-dose score | 78 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 1, pre-dose score | 130 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 1, post-dose score | 180 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 2, pre-dose score | 76 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 2, post-dose score | 50 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 3, pre-dose score | 192 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 3, post-dose score | 277 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 4, pre-dose score | 25 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 4, post-dose score | 135 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 5, pre-dose score | 55 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 5, post-dose score | 2 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 6, pre-dose score | 145 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 6, post-dose score | 20 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 7, pre-dose score | 22 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 7, post-dose score | 7 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 8, pre-dose score | 183 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 8, post-dose score | 123 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 9, pre-dose score | 278 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 9, post-dose score | 289 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT: Participant 10, pre-dose score | 73 scores on a scale |
| Part A: Dabrafenib 75 mg | Part B: Pre- and Post-dose H-scores for Individual Participants | p-AKT, Participant 10, post-dose score | 0 scores on a scale |
Secondary
Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib
Pre-dose (trough) concentration at the end of the dosing interval (Ctau) and maximum plasma concentration (Cmax) were assessed for plasma dabrafenib (DAB) following repeat dosing of DAB administered in combination with trametinib (T). The trough concentration is defined as the plasma level of a pharmaceutical product measured just before the next dose. Blood samples for PK analysis of the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Time frame: Day 15 and Day 21
Population: PK Population. Only those participants who were available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 15 | 72.9 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 15 | 640 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 15 | 59.8 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 15 | 399 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 15 | 2345 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 15 | 3757 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 15 | 257 ng/mL |
| Part A: Dabrafenib 75 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 15 | 300 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 15 | 906 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 21 | 1263 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 15 | 355 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 15 | 47.8 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 21 | 136 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 15 | 418 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 21 | 775 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 15 | 2360 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 21 | 2920 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 21 | 543 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 15 | 4545 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 21 | 5301 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 15 | 249 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 21 | 196 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 15 | 44.6 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 21 | 185 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 15 | 597 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 21 | 102 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 21 | 668 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 21 | 248 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 15 | 2792 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 21 | 3221 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 15 | 115 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 15 | 4636 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 21 | 5416 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 15 | 1306 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 21 | 1346 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 21 | 373 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 15 | 97.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 15 | 331 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 21 | 92.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 15 | 523 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 21 | 82.7 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Ctau, Day 15 | 74.4 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 15 | 1046 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 21 | 722 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 15 | 460 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 21 | 6257 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Cmax, Day 15 | 630 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 15 | 4372 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 21 | 369 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Cmax, Day 21 | 1391 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Ctau, Day 21 | 3740 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 21 | 79.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Ctau, Day 15 | 318 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Cmax, Day 21 | 430 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Cmax, Day 15 | 7098 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) and Maximum Plasma Concentration (Cmax) of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Ctau, Day 15 | 73.7 ng/mL |
Secondary
Part B: Progression-free Survival (PFS) as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma
PFS is defined as the interval between the first dose of study medication and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm. BRAFi-naïve were the participants with BRAF-mutation positive melanoma who had not received prior therapy with a BRAF-inhibitor..
Time frame: From the date of first dose to the earliest date of disease progression (PD) or death due to any cause (up to approximately 8 years)
Population: All Treated Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Progression-free Survival (PFS) as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 8.7 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Progression-free Survival (PFS) as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 8.2 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Progression-free Survival (PFS) as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 5.4 Months |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Progression-free Survival (PFS) as Assessed by the Investigator in Participants With BRAFi-naïve Mutant Metastatic Melanoma | 10.8 Months |
Secondary
Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib
The tmax is defined as the time of occurenceof Cmax. Tha tmax was assessed for plasma dabrafenib (DAB) following repeat dosing of dabrafenib 75 and 150 mg BID administered in combination with trametinib. Blood samples for PK analysis of the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Time frame: Day 15 and Day 21
Population: PK Population. Only those participants who were available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 15 | 2.00 Hours |
| Part A: Dabrafenib 75 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 15 | 2.00 Hours |
| Part A: Dabrafenib 75 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 15 | 6.00 Hours |
| Part A: Dabrafenib 75 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 15 | 0.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 21 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 21 | 4.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 15 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 15 | 4.96 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 21 | 1.54 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 15 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 15 | 2.94 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 21 | 1.97 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 15 | 4.17 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 21 | 1.53 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 15 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 21 | 1.01 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 21 | 4.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 15 | 4.17 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 15 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 21 | 4.02 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 21 | 1.50 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 15 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 15 | 1.50 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2167542 Day 15 | 1.52 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2298683 Day 15 | 4.10 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | GSK2285403 Day 21 | 2.07 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib | DAB Day 21 | 2.04 Hours |
Secondary
Part C: Oral Clearance (CL/F) of Dabrafenib and Trametinib
Oral clearance (CL/F) of dabrafenib and trametinib were assessed using a population approach. Oral clearance (CL/F) is defined as the apparent volume of plasma in the vascular compartment cleared of drug per unit time by the processes of metabolism and excretion. For dabrafenib, population CL/F is defined as inducible and non-inducible CL/F. As dabrafenib induces its own metabolism, total oral clearance at steady state includes a non-induced (Day 1) component and an induced component, as estimated by a population PK model.
Time frame: Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48
Population: PK Population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C: Oral Clearance (CL/F) of Dabrafenib and Trametinib | Non-inducible | 19.4 Liters per hour (L/hr) |
| Part A: Dabrafenib 75 mg | Part C: Oral Clearance (CL/F) of Dabrafenib and Trametinib | Inducible | 20.0 Liters per hour (L/hr) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Oral Clearance (CL/F) of Dabrafenib and Trametinib | Non-inducible | 5.07 Liters per hour (L/hr) |
Secondary
Part C: Oral Volume of Distribution (V/F) of Dabrafenib and Trametinib
Oral volume of distribution (V/F) of dabrafenib and trametinib were assessed using a population approach. Oral volume of distribution (V/F) is defined as the apparent volume of distribution in the central compartment.
Time frame: Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part C: Oral Volume of Distribution (V/F) of Dabrafenib and Trametinib | 80.8 Liters (L) |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Oral Volume of Distribution (V/F) of Dabrafenib and Trametinib | 184 Liters (L) |
Secondary
Part C: Plasma Concentrations of Dabrafenib and Its Metabolites
Plasma concentrations of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were assesed following daily dose of dabrafenib and trametinib.
Time frame: Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 56
Population: PK Population. Only those participants who were available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2285403 | 92.7 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2118436 | 45.6 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2118436 | 84.4 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2118436 | 66.3 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2118436 | 40.6 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2118436 | 229 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2118436 | 44.7 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2118436 | 46.4 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2118436 | 59.3 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2285403 | 65.2 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2285403 | 113.4 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2285403 | 95.0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2285403 | 62.5 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2285403 | 263.8 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2285403 | 43.3 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2285403 | 48.3 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2298683 | 3493 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2298683 | 3149.7 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2298683 | 3497.9 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2298683 | 2876.5 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2298683 | 2699.9 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2298683 | 4410.6 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2298683 | 3554.9 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2298683 | 2032.2 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2167542 | 247.9 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2167542 | 239.5 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2167542 | 244 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2167542 | 225.6 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2167542 | 171 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2167542 | 222.2 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2167542 | 204.5 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2167542 | 171.8 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2298683 | 3694.7 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2118436 | 68.2 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2285403 | 143.5 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2298683 | 3043.3 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2118436 | 69.8 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2285403 | 86.7 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2167542 | 232 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2118436 | 66.7 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2298683 | 3238.4 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2298683 | 4146.9 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2118436 | 66.2 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2167542 | 250 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2167542 | 247.2 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2118436 | 57.1 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2298683 | 2946.1 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2285403 | 93.6 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2118436 | 97.6 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2285403 | 88.1 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2298683 | 3843.5 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2118436 | 105.6 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2298683 | 3365.4 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2167542 | 204.4 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2118436 | 44.5 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2285403 | 92.9 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2167542 | 249.3 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2285403 | 71.8 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2298683 | 3267.1 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2167542 | 288 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2285403 | 80.4 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2167542 | 275.2 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2167542 | 255.4 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2285403 | 81.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2118436 | 193.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2167542 | 268.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2285403 | 130.2 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2285403 | 87.4 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2167542 | 262.4 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2285403 | 136.2 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2285403 | 146.4 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2285403 | 141.5 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2167542 | 243.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2298683 | 3145.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2298683 | 3010 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2298683 | 2756.5 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2167542 | 254.6 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2298683 | 3193.7 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2167542 | 260.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2298683 | 3046.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2118436 | 66.3 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2298683 | 3492.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2118436 | 50.5 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2167542 | 289.3 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2118436 | 82.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 24, GSK2118436 | 93.3 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2298683 | 3936.1 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 32, GSK2118436 | 66.4 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2167542 | 462.1 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 40, GSK2118436 | 150.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 48, GSK2118436 | 107.7 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 56, GSK2298683 | 2904.9 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 16, GSK2285403 | 114.7 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2285403 | 90.5 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Week 8, GSK2285403 | 90.6 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Dabrafenib and Its Metabolites | Day 15, GSK2167542 | 289.3 ng/mL |
Secondary
Part C: Plasma Concentrations of Trametinib
Plasma concentrations of trametinib was assessed following daily dose of dabrafenib and trametinib.
Time frame: Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 56
Population: PK Population. Only those participants who were available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Day 15 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 8 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 16 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 24 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 32 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 40 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 48 | 0 ng/mL |
| Part A: Dabrafenib 75 mg | Part C: Plasma Concentrations of Trametinib | Week 56 | 0 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 16 | 6.99 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 48 | 5.62 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 24 | 5.99 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 32 | 5.77 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 40 | 7.11 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Day 15 | 5.86 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 8 | 6.70 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C: Plasma Concentrations of Trametinib | Week 56 | 9.90 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 16 | 9.87 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 8 | 10.3 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Day 15 | 9.35 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 24 | 9.54 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 48 | 10.3 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 40 | 10.1 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 32 | 9.74 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C: Plasma Concentrations of Trametinib | Week 56 | 8.60 ng/mL |
Secondary
Part C (Randomized): Overall Survival (OS)
OS is defined as the interval of time between the date of randomization until the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact. When calculating overall survival, deaths following crossover were included.
Time frame: From the date of randomization until date of death due to any cause (up to approximately 7 years)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part C (Randomized): Overall Survival (OS) | 20.2 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part C (Randomized): Overall Survival (OS) | 18.7 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part C (Randomized): Overall Survival (OS) | 25.0 Months |
Secondary
Part D: Area Under the Concentration-time Curve Assessment of Trametinib
AUC(0-tau) after single and repeat dose of teametinib alone and in combination with dabrafenib was observed at Day 1 and Day 21. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.Participants receiving DAB 75 mg to DAB 75 mg + Trametinib 2 mg and those receiving DAB 150 mg to DAB 150 mg + Trametinib 2 mg did not receive Trametinib until Day 29; therefore, AUC(0-tau) was not analyzed in these participants at Days 1 and 21.
Time frame: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose
Population: PK Population. Only participants who were available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve Assessment of Trametinib | Day 1 | 53.4 ng*h/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve Assessment of Trametinib | Day 21 | 366 ng*h/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve Assessment of Trametinib | Day 1 | 50.7 ng*h/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve Assessment of Trametinib | Day 21 | 356 ng*h/mL |
Secondary
Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites
Area under the concentration-time curve (AUC) from pre-dose to dosing interval (AUC\[0-tau\]), from pre-dose to the last time of quantifable concentration (AUC\[0-tau\]), and from pre-dose extrapolated to infinity (AUC\[0-inf\]) of DAB metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) after single and repeat doses of DAB alone and in combination with trametinib was measured at Day 1 and Day 21.
Time frame: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose
Population: PK Population. Only participants who were available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 1 | 132 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-tau), Day 21 | 34283 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 21 | 1775 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC, (0-tau), Day 1 | 10396 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC (0-tau), Day 21 | 2568 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-inf), Day 1 | 3963 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-t) Day 1 | 500 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-t), Day 1 | 20047 ng*hr/mL |
| Part A: Dabrafenib 75 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-tau), Day 1 | 3134 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-t), Day 1 | 35206 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 1 | 190 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-tau), Day 21 | 59340 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-inf), Day 1 | 7415 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-tau), Day 1 | 5950 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC (0-tau), Day 21 | 4262 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 21 | 2707 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-t) Day 1 | 737 ng*hr/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC, (0-tau), Day 1 | 15952 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-t), Day 1 | 22692 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-tau), Day 1 | 3694 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-inf), Day 1 | 5026 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC (0-tau), Day 21 | 2919 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC, (0-tau), Day 1 | 9575 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-tau), Day 21 | 39672 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 1 | 88.8 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-t) Day 1 | 614 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 21 | 2508 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 1 | 354 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC, (0-tau), Day 1 | 20935 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC (0-tau), Day 21 | 4216 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-tau), Day 21 | 3632 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2167542, AUC(0-t) Day 1 | 1316 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-inf), Day 1 | 7907 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-tau), Day 21 | 52712 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2298683, AUC (0-t), Day 1 | 31666 ng*hr/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Area Under the Concentration-time Curve (AUC) of Dabrafenib Metabolites | GSK2285403, AUC(0-tau), Day 1 | 6524 ng*hr/mL |
Secondary
Part D: Cmax Assessment of Trametinib
Cmax of trametinib after single and repeat dose in combination with DAB was observed at Day 1 and Day 21. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.Participants receiving DAB 75 mg to DAB 75 mg + Trametinib 2 mg and those receiving DAB 150 mg to DAB 150 mg + Trametinib 2 mg did not receive Trametinib until Day 29; therefore, Cmax was not analyzed in these participants at Days 1 and 21.
Time frame: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose
Population: PK Population. Only participants who were available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax Assessment of Trametinib | Day 1 | 6.8 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax Assessment of Trametinib | Day 21 | 24.1 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax Assessment of Trametinib | Day 1 | 6.6 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax Assessment of Trametinib | Day 21 | 22.6 ng/mL |
Secondary
Part D: Cmax of Dabrafenib Metabolites
The maximum concentration (Cmax) of dabrafenib metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) after single and repeat doses of DAB alone and in combination with trametinib was measured at Day 1 and Day 21.
Time frame: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose
Population: PK Population. Only participants who were available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 525 ng/mL |
| Part A: Dabrafenib 75 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 596 ng/mL |
| Part A: Dabrafenib 75 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 1475 ng/mL |
| Part A: Dabrafenib 75 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 3637 ng/mL |
| Part A: Dabrafenib 75 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 50.1 ng/mL |
| Part A: Dabrafenib 75 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 210 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 355 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 6743 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 1055 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 2268 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 1203 ng/mL |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 68.6 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 696 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 1478 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 4158 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 289 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 61.2 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 597 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 86.3 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 440 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 1120 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 6319 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 1363 ng/mL |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Cmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 2551 ng/mL |
Secondary
Part D: Duration of Response as Assessed by the Investigator
Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis.) 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 \[e.g., percent change from Baseline\]) is defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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 mm.
Time frame: First documented evidence of PR or CR until the earlier of date of disease progression or date of death due to any cause (up to approximately 7 years)
Population: ITT Population. Only those participants who had CR or PR were considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Duration of Response as Assessed by the Investigator | 8.2 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Duration of Response as Assessed by the Investigator | 10.1 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Duration of Response as Assessed by the Investigator | 5.9 Months |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Duration of Response as Assessed by the Investigator | 14.3 Months |
Secondary
Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants
Best overall response is defined as complete response (CR: the disappearance of all target lesions. Any pathological lymph nodes must be \<10 milimeter \[mm\] in the short axis.) or partial reponse (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 \[e.g., percent change from Baseline\]). To be assigned a status of PR or CR, a confirmatory disease assessment should be performed no less than 28 days after the criteria for response are first met. Response was evaluated by an investigator as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
Time frame: From the date of first dose of study medication to the first documented evidence of a confirmed complete response or partial response (up to approximately 7 years)
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | CR | 0 Participants |
| Part A: Dabrafenib 75 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | PR | 8 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | PR | 10 Participants |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | CR | 2 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | CR | 5 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | PR | 28 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | CR | 7 Participants |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Number of Participants With the Best Overall Response as Assessed by the Investigator in Participants | PR | 21 Participants |
Secondary
Part D: Overall Survival (OS)
OS is defined as the interval of time between the date of randomization until the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact.
Time frame: From the date of first dose until date of death due to any cause (up to approximately 7 years)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Overall Survival (OS) | 19.5 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Overall Survival (OS) | 15.5 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Overall Survival (OS) | 15.3 Months |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Overall Survival (OS) | 40.3 Months |
Secondary
Part D: Progression-free Survival (PFS) as Assessed by the Investigator
PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. 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 mm.
Time frame: From the date of randomization to the earliest date of disease progression (PD) or death due to any cause (up to approximately 7 years)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Progression-free Survival (PFS) as Assessed by the Investigator | 7.9 Months |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Progression-free Survival (PFS) as Assessed by the Investigator | 9.3 Months |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Progression-free Survival (PFS) as Assessed by the Investigator | 7.4 Months |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Progression-free Survival (PFS) as Assessed by the Investigator | 11.1 Months |
Secondary
Part D: Tmax Assessment of Trametinib
The tmax of trametinib after single and repeat dose in combination with dabrafenib (DAB) was observed at Day 1 and Day 21. Blood samples for PK analysis of dabrafenib were obtained at pre-dose Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (Day 1 only) post-dose administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin.Participants receiving DAB 75 mg to DAB 75 mg + Trametinib 2 mg and those receiving DAB 150 mg to DAB 150 mg + Trametinib 2 mg did not receive Trametinib until Day 29; therefore, tmax was not analyzed in these participants at Days 1 and 21.
Time frame: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose
Population: PK Population. Only participants who were available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax Assessment of Trametinib | Day 1 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax Assessment of Trametinib | Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax Assessment of Trametinib | Day 1 | 1.50 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax Assessment of Trametinib | Day 21 | 2.00 Hours |
Secondary
Part D: Tmax of Dabrafenib Metabolites
The time to Cmax (tmax) of DAB metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) after single and repeat doses of DAB alone and in combination with trametinib was measuered at Day 1 and Day 21.
Time frame: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose. Day 21: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dose
Population: PK Population. Only participants who were available at the indicated timepoints were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Dabrafenib 75 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 3.00 Hours |
| Part A: Dabrafenib 75 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 2.00 Hours |
| Part A: Dabrafenib 75 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 10.0 Hours |
| Part A: Dabrafenib 75 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 5.00 Hours |
| Part A: Dabrafenib 75 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 24.0 Hours |
| Part A: Dabrafenib 75 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 0.75 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 8.93 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 3.51 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 24.0 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 2.00 Hours |
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 4.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 10.0 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 5.98 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 24.0 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 3.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 1 | 24.0 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 21 | 4.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 21 | 2.00 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2285403, Day 1 | 2.07 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2167542, Day 21 | 1.75 Hours |
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | Part D: Tmax of Dabrafenib Metabolites | GSK2298683, Day 1 | 8.00 Hours |