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

• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features
• Must provide a core or excisional biopsy from soft tissue or bone biopsy from soft tissue within 1 year of screening and after developing mCRPC
• Has prostate cancer progression within 6 months prior to screening by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on RECIST criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.
• Ongoing androgen deprivation with serum testoterone <50ng/dL
• Stable doses of bone resorptive therapy
• ECOG PS 0-1
• Has previously received docetaxel for mCRPC. Prior treatment with one other chemotherapy is allowed. Up to 2 second-generation hormonal agents (eg. abiraterone, enzalutimide, etc.) are allowed. Prior ketoconazole is allowed. Docetaxel used more than once is considered as 1 therapy.
• No diagnosis of immunodeficiency or systemic steroid therapy
• No autoimmune disease within last 2 years
• No known HBV/HCV/HIV
• No known active CNS mets
• No superscan bone scan
• No active cardiovascular disease
• No gastrointestinal malabsortion
• No active hemoptysis

• Primary
  • Percentage of patients with decrease of >/= 50% in PSA
  • AE
  • ORR
• Secondary
  • DCR
  • OS
  • DOR
  • ORR based on PCWG3-modifeid RECIST
  • Time to PSA progression
  • Radiographic PFS
  • Composite Response Rate (PSA Decrease,, RECIST)