A 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 (KEYLYNK-010)

1. Have histologically or cytologically confirmed adenocarcinoma of the
prostate without small cell histology. The diagnosis must be stated in a
pathology report and confirmed by the investigator. 2. Have prostate cancer
progression while receiving androgen deprivation therapy (or post bilateral
orchiectomy) within 6 months before screening, as determined by the
investigator 3. Have disease progression under the following conditions if the
participant received anti-androgen therapy before screening: •*Evidence of
progression >4 weeks since the last flutamide treatment. •*Evidence of
progression >6 weeks since the last bicalutamide or nilutamide treatment. 4.
Have current evidence of metastatic disease documented by bone lesions on bone
scan and/or soft tissue disease shown by CT/MRI. 5. Have received prior
treatment with abiraterone acetate OR enzalutamide, but not both. 6. Have
received docetaxel chemotherapy regimen for mCRPC and have had PD during or
after treatment with docetaxel. If docetaxel chemotherapy has been used more
than once it will be considered as 1 therapy. Prior docetaxel for mCRPC is
allowed if >=4 weeks have elapsed from the last dose of docetaxel before Day 1
of Cycle 1. 7. Have ongoing androgen deprivation with serum testosterone <50
ng/dL (<2.0 nM). If the participant is currently being treated with
luteinizing hormone-releasing hormone (LHRH) agonists or antagonists (in
participants who have not undergone orchiectomy), this therapy must have been
initiated at least 4 weeks before the date of randomization, and treatment must
be continued throughout the study. 8. If receiving bone resorptive therapy,
including but not limited to bisphosphonates or denosumab, have been receiving
stable doses for >=4 weeks before the date of randomization. 9. Have adequate
organ function per central laboratory; as defined in the protocol 10. Be male.
11. Be >=18 years of age on the day of signing the informed consent. 12. Agree
to the use contraception during the intervention period and for the following
days after last dose of study intervention: - olaparib: 95 days - abiraterone
acetate: 7 days - enzalutamide: 30 days 13. Also agree to use a male condom
when engaging in any activity that allows passage of ejaculate to another
person of any sex. 14. The participant (or legally acceptable representative if
applicable) provides written informed consent/assent for the study. The
participant may also provide consent/assent for future biomedical research.
However, the participant may participate in the main study without
participating in future biomedical research. 15. Have 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; other exceptions may be considered after
Sponsor consultation. 16. Have an Eastern Cooperative Oncology Group (ECOG)
performance status of 0 or 1, assessed within 7 days of randomization.

1. Has a known additional malignancy that is progressing or has required active
treatment in the last 3 years. Participants with basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, or carcinoma in situ who have
undergone potentially curative therapy are not excluded. 2. Has myelodysplastic
syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of
MDS/AML. 3. Has persistent toxicities (CTCAE Grade >2) caused by previous
cancer therapy, excluding alopecia and neuropathy. 4. Has received
colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF],
granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant
erythropoietin) within 28 days prior to the date of randomization. 5. Is
considered a poor medical risk due to a serious uncontrolled medical disorder,
nonmalignant systemic disease, or active uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent
(within 3 months) myocardial infarction, uncontrolled major seizure disorder,
unstable spinal cord compression, superior vena cava syndrome, extensive
interstitial bilateral lung disease on high resolution computed tomography
scan, or any psychiatric disorder that prohibits obtaining informed consent. 6.
Has a known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the study. 7. Has an active autoimmune
disease that has required systemic treatment in the past 2 years. Replacement
therapy is not considered a form of systemic treatment. 8. Has a
gastrointestinal disorder affecting absorption. 9. Is unable to swallow
capsules/tablets. 10. Has a history of (noninfectious) pneumonitis requiring
steroids, or has current pneumonitis. 11. Has an active infection, including
tuberculosis, requiring systemic therapy. 12. Has a history or current evidence
of any condition, therapy, or laboratory abnormality that might confound the
results of the study, interfere with the participant*s participation for the
full duration of the study, or indicate that participation in the study is not
in the best interest of the participant, in the opinion of the treating
investigator. 13. Has known active human immunodeficiency virus (HIV),
hepatitis B virus (eg, hepatitis B surface antigen reactive) or hepatitis C
virus (HCV) infection (eg, HCV RNA [qualitative] is detected). 14. Has known
active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided
they are stable 15. Has a diagnosis of immunodeficiency or is receiving chronic
systemic steroid therapy (at doses exceeding 10 mg daily of prednisone
equivalent) or any other form of immunosuppressive therapy within 7 days prior
to the date of randomization. 16. Has (Grade >=3) hypersensitivity to
pembrolizumab and/or any of its excipients. 17. Has known hypersensitivity to
the components or excipients in olaparib, abiraterone acetate, prednisone or
prednisolone, or enzalutamide. 18. Has CTCAE Grade >=2 peripheral neuropathy,
except when due to trauma. 19. Has ascites or clinically significant pleural
effusion. 20. Has had a seizure or seizures within 6 months of signing the
informed consent or has any condition that may predispose to seizures. 21. Has
a history of loss of consciousness within 12 months of the screening visit. 22.
Has symptomatic congestive heart failure. 23. Has had a myocardial infarction
or uncontrolled angina within 6 months prior to the date of randomization. 24.
Has a history of clinically significant ventricular arrhythmias (eg,
ventricular tachycardia, ventricular fibrillation, or torsade de pointes). 25.
Has a history of Mobitz II second-degree or third-degree heart block without a
pacemaker in place. 26. Has hypotension as indicated by systolic blood pressure
(BP) <86 mmHg at the screening visit. 27. Has bradycardia as indicated by
heart rate <50 beats/minute on the screening electrocardiogram (ECG). 28.
Has uncontrolled hypertension as indicated by systolic BP >170 mmHg or
diastolic BP >105 mmHg at the screening visit. 29. Has received an
anticancer monoclonal antibody (mAb) before randomization. 30. Has received
prior treatment with olaparib or any other PARP inhibitor. 31. Has received
prior treatment with apalutamide or darolutamide. 32. Has received prior
treatment with abiraterone acetate for metastatic hormone-sensitive prostate
cancer. 33. Has undergone major surgery, including local prostate intervention
(except prostate biopsy), within 28 days prior to the date of randomization,
and has not recovered from the toxicities and/or complications. 34. Has used
herbal products that may have hormonal anti-prostate cancer activity and/or are
known to decrease PSA (eg, saw palmetto) before the date of randomization. 35.
Has received prior treatment with radium or other therapeutic
radiopharmaceuticals for prostate cancer. 36. Has received prior radiotherapy
within 2 weeks of the date of randomization. Participants must have recovered
from all radiation-related toxicities, must not require corticosteroids, and
must not have had radiation pneumonitis. A 1-week washout is permitted for
palliative radiation (<=2 weeks of radiotherapy) for non-CNS disease. 37. 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.
38. Has received prior targeted small molecule therapy within 4 weeks prior to
the date of randomization or has not recovered from AEs due to a previously
administered agent 39. Is currently receiving either strong or moderate
inhibitors of CYP3A4 that cannot be discontinued for the duration of the study.
The required washout period prior to starting olaparib is 2 weeks. 40. Is
currently receiving either strong or moderate inducers of CYP3A4 that cannot be
discontinued for the duration of the study. The required washout period prior
to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
41. Is currently being treated with CYP450-inducing antiepileptic drugs for
seizures. Use of antiepileptic drugs for pain control is allowed in
participants without seizures, unless these drugs are excluded due to CYP450
induction. 42. Has received 5α reductase inhibitors (eg, finasteride or
dutasteride), estrogens, or cyproterone within 4 weeks prior to the date of
randomization. 43. Has received a previous allogenic bone marrow transplant or
double umbilical cord transplantation (dUCBT). 44. Has received a whole blood
transfusion in the last 120 days prior to the date of randomization. Packed red
blood cells and platelet transfusions are acceptable if not given within 28
days of the date of randomization. 45. Has received a live vaccine within 30
days before the date of randomization. 46. Is currently participating in or has
participated in a study of an investigational agent, or has used an
investigational device, before the date of randomization. 47. Has a resting ECG
indicating uncontrolled, potentially reversible cardiac conditions as judged by
the investigator 48. Has a bone *superscan,* 49. Is expecting to father
children within the projected duration of the study, starting with the
screening visit through the duration after the last dose of study intervention
listed in inclusion criterion #12