Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)

Inclusion Criteria:

• Male participants with histologically- or cytologically-confirmed adenocarcinoma ofthe prostate without small cell histology

• Has metastatic disease assessed by investigator and verified by BICR by either ≥2bone lesions on bone scan and/or visceral disease by computed tomography/magneticresonance imaging (CT/MRI)

• Willing to maintain continuous Androgen Deprivation Therapy (ADT) with aluteinizing-hormone releasing hormone (LHRH) agonists or antagonists during studytreatment or have a history of bilateral orchiectomy

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1assessed within 10 days of randomization

• Participants receiving bone resorptive therapy (including, but not limited to,bisphosphonate or denosumab) must have been on stable doses prior to randomization

• Has adequate organ function

• Has provided newly obtained core or excisional biopsy (obtained within 12 months ofscreening) from soft tissue not previously irradiated (samples from tumorsprogressing in a prior site of radiation are allowed). Participants with bone onlyor bone predominant disease may provide a bone biopsy sample

• Male participants must agree to the following during the intervention period and forat least 120 days after the last dose of study intervention: Refrain from donatingsperm PLUS either be abstinent from heterosexual intercourse and agree to remainabstinent OR agree to use contraception, unless confirmed to be azoospermic

• Male participants must agree to use male condom when engaging in any activity thatallows for passage of ejaculate to another person of any sex

Exclusion Criteria:

• Has a known additional malignancy that is progressing or has required activetreatment in the last 3 years

• Has an active autoimmune disease that has required systemic treatment in past 2years

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

• Has undergone major surgery including local prostate intervention (excludingprostate biopsy) within 28 days prior to randomization and not recovered adequatelyfrom the toxicities and/or complications

• Has a gastrointestinal disorder affecting absorption or is unable to swallowtablets/capsules

• Has an active infection (including tuberculosis) requiring systemic therapy

• Has a history of (non-infectious) pneumonitis that required steroids or has currentpneumonitis

• Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) orhepatitis C virus (HCV) infection

• Has known or suspected central nervous system (CNS) metastases and/or carcinomatousmeningitis

• 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 had myocardial infarction or uncontrolled angina within 6 months prior torandomization, or has New York Heart Association class III or IV congestive heartfailure or a history of New York Heart Association class III or IV congestive heartfailure

• Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) oruncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic bloodpressure >105 mmHg) at the screening visit

• Has a history of clinically significant ventricular arrhythmias

• Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of theirexcipients

• Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostatecancer for >39 months in duration or within 9 months prior to randomization or withevidence of disease progression while receiving ADT

• Has had prior treatment with a next generation hormonal agent (eg, abiraterone,enzalutamide, apalutamide, darolutamide)

• Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed celldeath-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatoryor coinhibitory T-cell receptor

• Has received a live vaccine within 30 days prior to randomization

• Has a "superscan" bone scan

• Has had an allogenic tissue/solid organ transplant

• Is expecting to conceive or father children within the projected duration of thestudy, starting with the screening visit through 120 days after the last dose ofstudy treatment

• Has received any prior pharmacotherapy, radiation therapy or surgery for metastaticprostate cancer with the following exceptions:

1. Up to 3 months of ADT or orchiectomy with or without concurrentfirst-generation antiandrogens, if patient was not treated with docetaxel

2. May have 1 course of palliative radiation or surgical therapy to treat symptomsresulting from metastatic disease if it was administered at least 4 weeks priorto randomization

3. For participants with low volume metastatic disease, may have 1 course ofdefinitive radiotherapy if it was administered at least 4 weeks prior torandomization

4. Up to 6 cycles of docetaxel therapy with final treatment administrationcompleted within 2 months of randomization and no evidence of diseaseprogression. In these participants up to 6 months of ADT permitted