KEYNOTE-991: This phase III trial is trying to understand the safety and effectiveness of using an immunotherapy (pembrolizumab) and hormone therapy (Enzalutamide plus androgen deprivation therapy) to treat patients with metastatic hormone sensitive prostate cancer (mHSPC)A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

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 past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
• Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
• Has an active infection (including tuberculosis) requiring systemic therapy
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Has known or suspected 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 had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
• Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >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 their excipients
• Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence 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 cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or 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 the study, starting with the screening visit through 120 days after the last dose of study treatment

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

  1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
  2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
  3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
  4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted