Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)

Official Title

Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365)


The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in patients with metastatic castrate resistant prostate cancer (mCRPC). There will be nine cohorts in this study: Cohort A will receive pembrolizumab + olaparib, Cohort B will receive pembrolizumab + docetaxel + prednisone, Cohort C will receive pembrolizumab + enzalutamide, Cohort D will receive pembrolizumab + abiraterone + prednisone Cohort E will receive pembrolizumab+lenvatinib, Cohort F will receive pembrolizumab+lenvatinib, Cohort G will receive pembrolizumab/vibostolimab coformulation (MK-7684A), Cohort H will receive pembrolizumab/vibostolimab coformulation, and Cohort I will receive pembrolizumab+carboplatin+etoposide in Arm 1 and carboplatin+etoposide in Arm 2. Outcome measures will be assessed individually for each cohort.

Trial Description

Primary Outcome:

  • Percentage of Participants With a Decrease of ≥50% in Prostatic Specific Antigen (PSA)
  • Number of Participants with Adverse Events (AEs)
  • Number of Participants Discontinuing Study Drug Due to AEs
  • Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
Secondary Outcome:
  • Disease Control Rate (DCR) Based on Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 Assessed by BICR
  • Overall Survival (OS)
  • Duration of Response (DOR) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
  • ORR Based on PCWG3-modified RECIST 1.1 Assessed by BICR
  • Time to PSA Progression
  • Radiographic Progression-free Survival (rPFS) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
  • Composite Response Rate Defined as Any One of the Following: A. Response Based on RECIST 1.1; B. PSA Decrease of ≥50%; or C. Circulating Tumour-cell Count Conversion (Pembrolizumab + Olaparib Cohort Only)
  • ORR Based on PCWG3-modified RECIST 1.1 Criteria Assessed by BICR
Assignment of patients to a cohort will be based on prior treatment as outlined in the eligibility criteria.

Participants who discontinue pembrolizumab or vibostolimab+pembrolizumab after 35 infusions for reasons other than disease progression or intolerability, or who discontinue pembrolizumab or coformulation of pembrolizumab/vibostolimab after attaining a complete response (and had at least 8 administrations of pembrolizumab or pembrolizumab/vibostolimab coformulation and at least 2 treatments with pembrolizumab or pembrolizumab/vibostolimab coformulation beyond initial complete response) may be eligible to receive a second course of treatment that includes up to 17 additional infusions (approximately 1 year) of pembrolizumab monotherapy or pembrolizumab/vibostolimab coformulation after they have experienced radiographic disease progression after stopping first course treatment.

Effective with Protocol Amendment 08, enrollment into Cohorts A, B, C, and D was closed.

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Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society