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 four cohorts in this study with 70 participants enrolled in each cohort: Cohort A will receive pembrolizumab + olaparib, Cohort B will receive pembrolizumab + docetaxel + prednisone, Cohort C will receive pembrolizumab + enzalutamide, and cohort D will receive pembrolizumab + abiraterone + prednisone. 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. Participants assigned to Cohort A must have previously received docetaxel for mCRPC. Participants assigned to Cohort B must have previously received either abiraterone acetate or enzalutamide (but not both) in the pre-chemotherapy mCRPC state. Participants assigned to Cohort C must have previously received abiraterone acetate in the pre-chemotherapy mCRPC state (prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks have elapsed from the last dose of docetaxel). Participants assigned to Cohort D must have not received chemotherapy for mCRPC and have either 1) not had prior second generation hormonal manipulation for mCRPC or 2) previously been treated with enzalutamide for mCRPC and failed treatment or become intolerant of the drug.

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