Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A)

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Histologically or cytologically confirmed diagnosis of adenocarcinoma of theprostate without small cell histology.

• Prostate cancer progression and received androgen deprivation therapy (ADT) or postbilateral orchiectomy within 6 months before screening.

• Evidence of disease progression from either, >4 weeks from last flutamide treatment,or >6 weeks from last bicalutamide or nilutamide treatment, if receiving firstgeneration anti-androgen therapy as last treatment therapy.

• Current evidence of metastatic disease.

• Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, ormetastatic, hormone-sensitive prostate cancer or castration-resistant prostatecancer and have disease progression during or after treatment.

• Treatment with bone resorptive therapy (including, but not limited to,bisphosphonate or denosumab) must have been on stable doses for >4 weeks beforerandomization.

• Participants who experienced adverse events (AEs) due to previous anticancertherapies must have recovered to <Grade 1 or baseline.

• Human immunodeficiency virus (HIV)-infected participants must have well controlledHIV on antiretroviral therapy.

• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible ifthey have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks,and have undetectable HBV viral load.

• Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• History of pituitary dysfunction.

• Poorly controlled diabetes mellitus.

• Active or unstable cardio/cerebro-vascular disease, including thromboembolic eventsand history of stroke or transient ischemic attack within 6 months before the firstdose of study intervention, history of myocardial infarction within 6 months beforethe first dose of study intervention, New York Heart Association Class III or IVcardiac disease or congestive heart failure, coronary heart disease that issymptomatic, or unstable angina

• History or family history of long corrected QT interval (QTc) syndrome.

• Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestiveof MDS/AML.

• History or current condition of adrenal insufficiency.

• History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.

• HIV-infected participants with a history of Kaposi's sarcoma and/or MulticentricCastleman's Disease.

• Undergone major surgery, including local prostate intervention (except prostatebiopsy) within 28 days before randomization, and has not recovered from thetoxicities and/or complications.

• Is on an unstable dose of thyroid hormone therapy within 6 months prior to firstdose of study intervention.

• Received a whole blood transfusion in the last 120 days before randomization (packedred blood cells and platelet transfusions are acceptable if not given within 28 daysbefore randomization).

• Received prior systemic anticancer therapy including investigational agents within 4weeks before randomization.

• Received prior radiotherapy within 2 weeks of start of study intervention orradiation-related toxicities, requiring corticosteroids.

• Received a live or live-attenuated vaccine within 30 days before the first does ofstudy intervention. Administration of killed vaccines is allowed.

• Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, orany other form of immunosuppressive therapy, within 7 days prior to the first doseof study intervention.

• Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years.

• Known active central nervous system (CNS) metastases and/or carcinomatousmeningitis.

• Active autoimmune disease that has required systemic treatment in the past 2 years.

• Active infection requiring systemic therapy.

• Concurrent active HBV or HCV infections.