Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Mevrometostat (PF-06821497) with Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer (MEVPRO-3)

Description
This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.

Objective
Primary:
--To demonstrate that mevrometostat in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging BICR assessed rPFS

Secondary:
- To demonstrate that mevrometostat in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging OS
- To compare anti-tumor activity between mevrometostat in combination with enzalutamide and placebo in combination with enzalutamide
- To compare safety and tolerability between mevrometostat in combination with enzalutamide and placebo in combination with enzalutamide
- To evaluate the PK of mevrometostat when dosed in combination with enzalutamide
- To compare PROs between mevrometostat in combination with enzalutamide and placebo in combination with enzalutamide
- To assess the relationship between ctDNA burden and outcome

Treatment This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCRPC where no systemic anti-cancer treatments have been initiated after documentation of mCRPC with the exception of ADT (androgen deprivation therapy) and first-generation anti-androgen agents. Prior treatment with any of the ARSi's enzalutamide, darolutamide, apalutamide, or abiraterone acetate, is not permitted in any setting. Chemotherapy is permitted in the castrate sensitive setting.

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) PF-06821497 in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.

Key Eligibility Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.

Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.

Progressive disease in the setting of medical or surgical castration.

ECOG performance status 0 or 1, with a life expectancy of >/=12 months as assessed by the investigator.

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital