This trial is active, not recruiting.

Conditions renal cell carcinoma, melanoma
Treatments pembrolizumab, pegifn-2b, ipilimumab
Phase phase 1/phase 2
Targets PD-1, CTLA-4
Sponsor Merck Sharp & Dohme Corp.
Start date March 2014
End date April 2017
Trial size 343 participants
Trial identifier NCT02089685, 2013-004072-36, 3475-029


This study is being done to analyze the safety, tolerability, and efficacy of treatment for advanced melanoma (MEL) and renal cell carcinoma (RCC) using combination regimens of pembrolizumab + pegylated interferon alfa-2b (PegIFN-2b) and pembrolizumab + ipilimumab (IPI). The primary hypothesis is that these combinations will be sufficiently well-tolerated to permit continued clinical investigation.

United States Texas
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Participants receive pembrolizumab intravenously (IV) at assigned dose every 3 weeks + PegIFN-2b subcutaneously (SC) at assigned dose once a week in each 6-week cycle.
Participants receive pembrolizumab IV at assigned dose every 3 weeks + IPI IV at assigned dose every 3 weeks for a total of two 6-week cycles.
Participants receive pembrolizumab IV monotherapy at assigned dose and schedule.

Primary Outcomes

Number of participants with dose-limiting toxicities (Part 1)
time frame: Up to 6 weeks (Cycle 1)
Number of participants experiencing adverse events (AEs)
time frame: Up to 2 years
Number of participants discontinuing study drug because of AEs
time frame: Up to 2 years
Progression-free survival (PFS)
time frame: Up to 2 years

Secondary Outcomes

Overall Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Response
time frame: Up to 2 years
Objective response rate (ORR) (Part 1B)
time frame: Up to 2 years
ORR (Part 2)
time frame: Up to 2 years
Duration of Response (DOR)
time frame: Up to 2 years
Overall Survival (OS)
time frame: Up to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically- or cytologically-confirmed diagnosis of advanced/unresectable or metastatic MEL or RCC (Part 1 only) with predominantly clear cell elements - MEL subjects may be treatment naïve or may have received prior lines of therapy for metastatic disease - RCC subjects must have received >=1 prior line of therapy for metastatic disease - Measurable disease as defined by RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate organ function - Resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 and/or recovered from major surgery or radiation therapy - Female participants of childbearing potential must be willing to use adequate contraception during the course of the study through 120 days after the last dose of study drug - Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study drug Exclusion Criteria - Uveal or ocular MEL - Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug - Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137 antibody, anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or other immune checkpoint inhibitor agents - Monoclonal antibody for direct antineoplastic treatment, prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or has not recovered from adverse events due to agents administered more than 4 weeks earlier - Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents - Active, non-infectious pneumonitis - Active infection requiring systemic therapy - Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial from screening through 120 days after the last dose of study drug - Prior therapy with interferon alfa (in adjuvant or metastatic settings) - Uncontrolled thyroid dysfunction - Uncontrolled diabetes mellitus. - Known history of human immunodeficiency virus (HIV) - Known active Hepatitis B or Hepatitis C - Received a live vaccine within 30 days prior to first dose of study drug

Additional Information

Official title A Phase I/II Clinical Trial to Study the Safety and Tolerability of MK-3475 + Pegylated Interferon Alfa-2b (PEG-IFN) and MK-3475 + Ipilimumab (IPI) in Subjects With Advanced Melanoma (MEL) and Renal Cell Carcinoma (RCC) (KEYNOTE 029)
Description The trial is being done in three parts: Part 1A will define the maximum tolerated dose (MTD)/maximum administered dose (MAD) for the drug combinations; a recommended Phase 2 dose (RP2D) for each combination will be identified. Part 1B (single arm expansion cohort) will better characterize safety and efficacy and provide preliminary efficacy data for the penbrolizumab + IPI combination in participants with MEL. Part 2 is a randomized portion of the trial and will evaluate preliminary efficacy of the drug combinations given in 6-week cycles for advanced MEL participants. Doses used in Part 2 will be decided by assessment of dose escalation cohorts in this study and external information.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..
Location data was received from the National Cancer Institute and was last updated in August 2016.