RecruitingInterventionalPhase 3

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

NCT ID: NCT07028853Sponsor: PfizerLast updated: 2026-06-10

Summary

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 and have not yet received chemotherapy in the mCSPC setting.

Detailed description

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.

Arms & interventions

DrugMevrometostat
Oral continuous
DrugPlacebo
Oral continuous
DrugEnzalutamide
Oral continuous

Outcome measures

Primary

Radiographic Progression Free Survival (rPFS)
rPFS is defined as the time from randomization until PD based on BICR assessment per RECIST v1.1 (soft tissue disease) and PCWG3 (bone disease), or death due to any cause, whichever occurs first.
Time frame: Randomization up to approximately 4 years

Secondary

Overall survival (OS)
Time frame: Randomization up to approximately 9 years
Objective response in measurable soft tissue disease
Time frame: Randomization up to approximately 4 years
Duration of Response (DoR) in measurable soft tissue disease
Time frame: Randomization up to approximately 4 years
Prostate Specific Antigen Response
Time frame: Randomization up to approximately 4 years
Time to prostate specific antigen (PSA) progression
Time frame: Randomization up to approximately 4 years
Time to initiation of antineoplastic therapy
Time frame: Randomization up to approximately 4 years
Time to first symptomatic skeletal event
Time frame: Randomization up to approximately 4 years
Time from randomization to CRPC
Time frame: Randomization up to approximately 4 years
Incidence of Adverse Events
Time frame: Randomization up to approximately 5 years
To evaluate the PK of mevrometostat when dosed in combination with enzalutamide
Time frame: Cycle 3 Day 1 to last PK draw at Cycle 5 Day 1 (cycle length is 28 days)
Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)
Time frame: Randomization up to approximately 5 years
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Time frame: Randomization up to approximately 5 years
Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P
Time frame: Randomization up to approximately 5 years
Patient-reported outcomes in cancer specific symptoms - time to definitive deterioration
Time frame: Randomization up to approximately 5 years
Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms per BFI
Time frame: Randomization up to approximately 5 years
Change from baseline in participant-reported general health status per EQ-5D-5L
Time frame: Randomization up to approximately 5 years
To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden
Time frame: Baseline up to approximately 4 years

Eligibility criteria

Sex: MaleAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (120)

Clearview Cancer Institute (Crestwood)

Huntsville, Alabama, 35801

Recruiting

Clearview Cancer Institute

Huntsville, Alabama, 35805

Recruiting