Please select the outcome measures that correspond to the clinical trial below.
Title: Phase I Study of Single Agent Pembrolizumab (MK-3475) in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma (KEYNOTE 001)
Brief Summary: The present study has 5 parts. In Parts A and A1, the dose of intravenous (IV) pembrolizumab (MK-3475) will be escalated from 1 to 10 mg/kg to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for participants with a histologically- or cytologically-confirmed diagnosis of any type of carcinoma or melanoma (MEL) by evaluating the Dose Limiting Toxicities (DLTs). Following completion of the dose escalation, additional patients will be enrolled in Part A2 to further define pharmacokinetic characteristics. Part B of the study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL and compare every 2 week dosing (Q2W) to every 3 week dosing (Q3W). Part C of the study will investigate the safety, tolerability, and efficacy of pembrolizumab administered at 10 mg/kg Q3W in participants with non-small cell lung carcinoma (NSCLC) that is locally advanced or metastatic. Part D of the study will investigate the low and high doses of study drug identified in Parts A and B (2 mg/kg and 10 mg/kg) administered Q3W in participants with advanced or metastatic MEL. Part E (closed with Amendment 7) was planned to investigate low, medium, and high doses of pembrolizumab in combination with standard chemotherapy in participants with locally advanced or metastatic NSCLC. Part F will investigate low and high doses of pembrolizumab (2 mg/kg and 10 mg/kg) administered Q2W or Q3W in treatment-naive and previously-treated participants with NSCLC with programmed cell death 1 ligand (PD-L1) gene expression. The primary hypotheses are the following: that pembrolizumab will have acceptable safety and tolerability; that pembrolizumab will show a clinically meaningful response rate (RR) or disease-control rate (DCR) in participants with melanoma (ipilimumab-refractory or not) and NSCLC, and that pembrolizumab will show a more clinically meaningful RR in participants with either cancer whose tumors express PD-L1.


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: Time to tumor progression (TTP) or death (progression free survival) after initiation of treatment. Tumor progression is defined per RECIST criteria. (6 weekly)
C: Recurrence Free Survival (RFS) (From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.)
D: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) in Participants With Solid Tumors (Parts A and A1) (Up to 28 days in Cycle 1); Number of Participants Who Experienced an Adverse Event (AE) (Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)); Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Integrated Radiology and Oncology (IRO): Melanoma Participants (Parts B Plus D) (Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)); ORR According to RECIST 1.1 as Assessed by Independent Review Committee (IRC): Non-Small Cell Lung Cancer (NSCLC) Participants (Parts C Plus F) (Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015))

Answer: D