Please select the outcome measures that correspond to the clinical trial below.
Title: An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the BRAF Inhibitor GSK2118436 in Combination With the MEK Inhibitor GSK1120212 in Subjects With BRAF Mutant Metastatic Melanoma
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.


Options:
A: Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib (Day 15); Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites (Day 15); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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)); 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); Part D (Analyte=GSK2118436): Tmax of a Single and Repeat Dose of Dabrafenib Alone and in Combination With Trametinib (Day 1 and Day 21); 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); 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)); 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)); 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)); 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)); 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)); 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))
B: Relapse-free survival (RFS) (Up to 1 year)
C: estimate BORR in patients with previously treated, therapy-refractory or -intolerant, Stage III (unresectable) or Stage IV melanoma receiving ipilimumab doses of 0.3, 3, and 10 mg/kg.
D: Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone (From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks))

Answer: A