This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve.

This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating mevrometostat in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCSPC who have not received systemic anticancer treatments with the exception of androgen-deprivation therapy (ADT) and first-generation antiandrogen agents. Prior therapy with up to 3 months of ADT (chemical or surgical) is allowed, with no radiographic evidence of disease progression or rising PSA levels prior to Day 1.

This study consists of a Screening Phase, Randomization, Treatment Phase, Safety Follow-up, and Long-Term Follow-up. Participants will be randomized on a 1:1 basis to receive (Arm A) mevrometostat (PF-06821497) in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.

Inclusion criteria

• Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
• Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
• Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
• Participants must have ECOG PS 0 or 1.

Exclusion criteria

• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Clinically significant cardiovascular disease.
• Known or suspected brain metastasis or active leptomeningeal disease.
• Participants must be treatment naïve at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC.
• Previous administration with an investigational product (drug or vaccine) within 30 days.
• Use of 5-alpha reductase inhibitors is prohibited within 28 days of randomization.
• Prior surgery from which the participant has not fully recovered at least 28 days prior to randomization
• Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
• Inadequate organ function.
• Known allergic or hypersensitivity reactions to mevrometostat or its excipients or to enzalutamide or its excipients.