Spots Global Cancer Trial Database for Study of Pembrolizumab (MK-3475) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001/KEYNOTE-001)

Study Description

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.

Detailed Description: Per protocol, all participants who were receiving study intervention or in survival follow-up could enroll in the extension study, KEYNOTE-587 (NCT03486873), which would allow further study participation after the Primary Completion Date cut-off. Thus, all efficacy outcome measures except for survival (Overall Survival \[OS\]) were to be followed up to the Interim Database cut-off of 18-Sept-2018, and the primary safety analyses (except for the DLT analysis) and Overall Survival were to be followed up to the study Primary Completion Date (Final Database cut-off of 05-Nov-2018). Five participants did not have end of study assessments completed by the Primary Completion Date cut-off and were subsequently followed up to the Study Completion Date (11-Dec-2018). End of treatment and end of study assessments are missing for these 5 and the status was noted as unknown as of the Primary Completion Date cut-off. Per protocol, any safety information after the Primary Completion Date cut-off (Final Database cut-off of 05-Nov-2018) would not be included in the safety analysis but reported by the Investigator to the Sponsor via the Sponsor Communication Form and filed in the electronic Trial Master File.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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