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8110 Gatehouse Road, Falls Church, VA 22042

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) (KEYNOTE-991)


General Information

Age Group




Protocol Number


Background Information

The purpose of this study is to test the safety of the study drugs, pembrolizumab (MK-3475) and enzalutamide when taken with the hormone drug androgen deprivation therapy (ADT).

The purpose of this study is also to see how well the study drugs pembrolizumab, enzalutamide, and ADT work together compared to placebo (a look-alike with no active ingredients), enzalutamide and ADT. The study is designed to discover if pembrolizumab taken with enzalutamide and ADT is more effective in slowing cancer growth and helps patients live longer than placebo taken with enzalutamide and ADT. An additional purpose of this study is to see if pembrolizumab in combination with enzalutamide and ADT helps patients have a better quality of life.

Principal Investigator

Inova Schar Cancer Institute
8081 Innovation Park Drive
Fairfax, VA 22031

A department of Inova Fairfax Hospital

Eligibility Information

  • Males over 18 years of age
  • Histologically- or cytologically-confirmed (if acceptable according to local health authority regulations) adenocarcinoma of the prostate without small cell histology
  • Metastatic disease as assessed by investigator and verified by BICR (prior to randomization) by either ≥2 bone lesions on bone scan and/or visceral disease (eg, lung or liver) by CT/MRI
  • Participant must be willing to maintain continuous ADT with a LHRH agonists or antagonists during study treatment or have a history of bilateral orchiectomy
  • An ECOG performance status of 0 or 1 assessed within 10 days of randomization
  • Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to randomization
  • Adequate organ function
  • Additional eligibility in protocol.

Ineligibility Information

  • 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 that have undergone potentially curative therapy are not excluded
  • An active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
  • Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
  • A gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer disease within last 3 months)
  • Known active HIV, hepatitis B virus (eg, hepatitis B surface antigen reactive) or HCV (eg, HCV RNA [qualitative] is detected). Testing for Hepatitis B and Hepatitis C is not required unless mandated by local regulation
  • Known or suspected CNS metastases and/or carcinomatous meningitis
  • Myocardial infarction, uncontrolled angina, congestive heart failure, significant ventricular arrhythmias, Mobitz II second degree or third degree heart block within 6 months prior to randomization
  • 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
  • Prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide).
  • Prior therapy 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 (eg, CTLA-4, OX-40, CD137)
  • Additional ineligibility in protocol.

Additional information: