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.

Phase 3

Not yet recruiting

• Conditions: Metastatic Castration Sensitive Prostate Cancer (mCSPC); Hormone Sensitive Prostate Cancer; Prostate Cancer; Cancer of the Prostate
• Interventions: Drug: Mevrometostat; Drug: Placebo; Drug: Enzalutamide

• Registration Number: NCT07028853
• Lead Sponsor: Pfizer

Brief 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.

Study Timeline

• Study First Submitted: 2025-04-15
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-11
• Study First Posted: 2025-06-19
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-02
• Study Start: 2025-08-25
• Primary Completion: 2028-09-12
• Study Completion: 2034-12-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Mevrometostat	Participants will receive mevrometostat/PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
Arm A	Enzalutamide	Participants will receive mevrometostat/PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
Arm B	Placebo	Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
Arm B	Enzalutamide	Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)

Primary Outcome Measures

Name	Time	Method
Radiographic Progression Free Survival (rPFS)	Randomization up to approximately 4 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Randomization up to approximately 9 years	OS defined as the time from the date of randomization until the date of death due to any cause.
Objective response in measurable soft tissue disease	Randomization up to approximately 4 years	The proportion of participants with measurable soft tissue disease at baseline who have a confirmed objective response of CR or PR per RECIST v1.1 will be summarized along with the 95% CI.
Duration of Response (DoR) in measurable soft tissue disease	Randomization up to approximately 4 years	The DoR is defined as the time from the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause whichever occurs first.
Prostate Specific Antigen Response	Randomization up to approximately 4 years	The proportion of participants with a 50% decline from baseline in PSA that is confirmed by a second consecutive value at least 21 days later in participants with detectable PSA values at baseline will be calculated for each treatment arm.
Time to prostate specific antigen (PSA) progression	Randomization up to approximately 4 years	Time from the date of randomization to the date of the first PSA progression.
Time to initiation of antineoplastic therapy	Randomization up to approximately 4 years	Time from randomization to first use of new antineoplastic therapy for prostate cancer.
Time to first symptomatic skeletal event	Randomization up to approximately 4 years	Time from randomization to first tumor-related symptomatic bone fracture, surgery or radiotherapy to the bone, and spinal cord compression, whichever occurs first.
Time from randomization to CRPC	Randomization up to approximately 4 years	Time from randomization to the first date of CRPC event.
Incidence of Adverse Events	Randomization up to approximately 5 years	Type, incidence, severity \[as graded by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v5.0\], seriousness and relationship to study medications of AEs.
To evaluate the PK of mevrometostat when dosed in combination with enzalutamide	Cycle 3 Day 1 to last PK draw at Cycle 5 Day 1 (cycle length is 28 days)	PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits.
Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)	Randomization up to approximately 5 years	Analysis of Brief Pain Inventory-Short Form (BPI-SF) will be based on the pain severity score (mean of individual BPI-SF items 3, 4, 5 and 6), the pain interference score (mean of items 9A-9G), and the single BPI-SF Item 3.
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Randomization up to approximately 5 years	Change from baseline in HRQoL (FACT-P total score) will be presented. The FACT-P total score will be calculated based on the participant responses to the 39 items in the FACT-P questionnaire.
Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P	Randomization up to approximately 5 years	Defined as the time from randomization to onset of definitive deterioration in FACT-P total score, which is defined as \>10 point decrease from baseline and no subsequent observations with a \<10 point decrease from baseline FACT-P total score
Patient-reported outcomes in cancer specific symptoms - time to definitive deterioration	Randomization up to approximately 5 years	Change from baseline and time to definitive deterioration in participant-reported prostate cancer specific functioning, and symptoms per EORTC QLQ-PR25
Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms per BFI	Randomization up to approximately 5 years	Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms (fatigue severity and fatigue interference) as per BFI.
Change from baseline in participant-reported general health status per EQ-5D-5L	Randomization up to approximately 5 years	Participants will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 possible responses that record the level of severity (no problems, slight problems, moderate problems, severe problems, or extreme problems) within each dimension.
To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden	Baseline up to approximately 4 years	Evaluation of ctDNA burden at baseline and on study.

Trial Locations

Locations (10)

Hokkaido University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Arizona Urology Specialists, PLLC; 🇺🇸 Tucson, Arizona, United States

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Chiba cancer center; 🇯🇵 Chiba-shi, Chiba, Japan

Kobe University Hospital; 🇯🇵 Kobe, Hyogo, Japan

Yokosuka Kyosai Hospital; 🇯🇵 Yokosuka, Kanagawa, Japan

Osaka University Hospital; 🇯🇵 Suita, Osaka, Japan

The University of Osaka Hospital; 🇯🇵 Suita, Osaka, Japan

Keio university hospital; 🇯🇵 Shinjuku-ku, Tokyo, Japan

National Hospital Organization Kumamoto Medical Center; 🇯🇵 Kumamoto, Japan