KEYLYNK-010: This phase III trial is assessing the safety and effectiveness of combining treatment with an oral targeted cancer drug (olaparib) and a type of immunotherapy (pembrolizumab) in patients with castrate-resistant prostate cancer that has spread to other parts of the body and not responded to prior treatmentsA Phase 3, Randomized Open-label Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Who Are Unselected for Homologous Recombination Repair Defects and Have Failed Prior Treatment With One Next-generation Hormonal Agent (NHA) and Chemotherapy

Exclusion

• Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (noninfectious) pneumonitis requiring steroids, or has current pneumonitis
• Has known active human immunodeficiency virus (HIV), hepatitis B virus (e.g., hepatitis B surface antigen reactive) or hepatitis C virus (HCV) infection (e.g., HCV RNA [qualitative] is detected)
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has a history of seizure or any condition that may predispose to seizure
• Has a history of loss of consciousness within 12 months of screening
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has (≥Grade 3) hypersensitivity to pembrolizumab and/or any of its excipients
• Has known hypersensitivity to the components or excipients in olaparib, abiraterone acetate, prednisone or prednisolone, or enzalutamide
• Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
• Has received an anticancer monoclonal antibody (mAb) before randomization
• Has received prior treatment with olaparib or any other PARP inhibitor
• Has received prior treatment with apalutamide or darolutamide
• Has received prior treatment with enzalutamide or apalutamide for metastatic hormone-sensitive prostate cancer
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA (e.g., saw palmetto) before the date of randomization
• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
• Has received prior treatment with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, or CD137)
• Is currently receiving either strong or moderate inhibitors of cytochrome P450 [CYP] (CYP3A4) that cannot be discontinued for the duration of the study
• Has received a previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT) or a solid organ transplant
• Has received a live vaccine within 30 days prior to the date of randomization
• Is currently participating in or has participated in a study of an investigational agent, or has used an investigational device, within 4 weeks before the date of randomization
• Has a bone "superscan"
• Is expecting to father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study intervention