Eligibility Details:
Inclusion Criteria:
- Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without
small cell histology
- Has prostate cancer progression while receiving androgen deprivation therapy (or post
bilateral orchiectomy) within 6 months prior to screening
- Has current evidence of metastatic disease documented by bone lesions on bone scan
and/or soft tissue disease shown by computed tomography/magnetic resonance imaging
(CT/MRI)
- Has received prior treatment with abiraterone acetate OR enzalutamide, but not both
- Have disease that progressed during or after treatment with abiraterone acetate
for either metastatic hormone-sensitive prostate cancer (mHSPC) or mCRP or
enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants
with bone progression)
- Participants that received abiraterone acetate for mHSPC may not have received
abiraterone acetate or enzalutamide for mCRPC
- Have received docetaxel chemotherapy regimen for mCRPC and have had progressive
disease during or after treatment with docetaxel
- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
- If receiving bone resorptive therapy, including but not limited to bisphosphonates or
denosumab, must have been receiving stable doses prior to randomization
- Must agree to refrain from donating sperm during the intervention period and for at
least 180 days thereafter PLUS Be abstinent from heterosexual intercourse OR Agree to
use contraception unless confirmed to be azoospermic AND Also agree to use a male
condom when engaging in any activity that allows passage of ejaculate to another
person of any sex
- Has provided tumor tissue from a fresh core or excisional biopsy (obtained within 12
months of screening) from soft tissue not previously irradiated. Samples from tumors
progressing at a prior site of radiation are allowed. Participants with bone-only or
bone-predominant disease may provide a bone biopsy sample
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed
within 7 days of randomization
Exclusion Criteria:
- 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) prior to 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) prior to 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 prior to 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 180 days after the last dose of study intervention
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
