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

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Must provide a core or excisional biopsy from soft tissue or bone biopsy within 1 year of screening and after developing mCRPC. Participants with bone metastasis only must provide an archival tumor tissue specimen.
• Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, 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. 
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
• Patients receiving bone resorptive therapy must be on stable doses
• ECOG PS 0-1
• Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide or other next-generation hormonal agents [NHA]) are allowed. Participants who received prior ketoconazole for metastatic disease may be enrolled. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. Prior docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC) is allowed if ≥4 weeks have elapsed from the last dose of docetaxel prior to Day 1 of Cycle 1
• No immunodeficiency or systemic steroid use
• No active autoimmune disease within 2 years
• No known HIV/HBV/HCV
• No known CNS mets
• No superscan bone scan
• No symptomatic ascites or pleural effusion

• Primary
  • Percentage of patients with PSA decrease of >/= 50%
  • AEs
  • ORR
• Secondary
  • DCR
  • OS
  • DOR
  • ORR by PCWG3-modified RECIST
  • Time to PSA progression
  • Radiographic PFS
  • Composite response rate (PFS, PSA)