A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF PF-06821497 (MEVROMETOSTAT) WITH ENZALUTAMIDE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MEVPRO-2)

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Pfizer (industry)

Phase: 3

Start date: Oct. 22, 2024

Planned enrollment: 900

Trial ID: NCT06629779
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: Mervometostat (EZH2i, PF-06821497)

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Goal: To determine whether adding the EZH2 inhibitor PF-06821497 (mevrometostat) to enzalutamide improves outcomes versus enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC) who are naïve to AR pathway inhibitors and abiraterone.

Patients: Adult men with histologically or cytologically confirmed prostate adenocarcinoma without small cell features, metastatic to bone and/or soft tissue, with progression in the castrate setting, ECOG 0–1 and life expectancy ≥12 months. Patients must be treatment-naïve in the mCRPC setting, allowing prior ADT and first-generation antiandrogens; docetaxel for mCSPC is permitted if no progression occurred during or within 3 months of completion. Key exclusions include clinically significant cardiovascular disease, active inflammatory GI disease or prior major gastric surgery, brain metastases or significant seizure history, recent or active suicidal ideation/behavior, prior myelodysplastic syndrome/AML or most other malignancies, prior ARSi, abiraterone, PARP inhibitor monotherapy, radioligand therapy, or other systemic therapy for mCRPC, recent investigational agents, and inadequate organ function.

Design: Global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial. Approximately 900 participants will be randomized 1:1 to experimental combination versus placebo control, with treatment, safety follow-up, and long-term follow-up phases.

Treatments: Arm A: PF-06821497 875 mg orally twice daily plus enzalutamide 160 mg once daily. Arm B: matching placebo twice daily plus enzalutamide 160 mg once daily. PF-06821497 (mevrometostat) is a potent, selective inhibitor of EZH2, the catalytic subunit of PRC2, reducing H3K27 methylation and reactivating silenced genes implicated in tumor growth and lineage plasticity. In early-phase studies in mCRPC, mevrometostat demonstrated manageable safety and signals of activity as monotherapy and with enzalutamide, including a reported median rPFS of about 17 months and objective responses in measurable disease. The rationale is to enhance ARSI benefit by epigenetic modulation via EZH2 inhibition. Enzalutamide is a standard androgen receptor signaling inhibitor that blocks AR nuclear translocation and transcriptional activity in mCRPC.

Outcomes: Primary endpoint: radiographic progression-free survival by BICR using RECIST v1.1 for soft tissue and PCWG3 for bone, or death. Key secondary endpoints include overall survival; time to pain progression (alpha protected); duration of response in measurable soft tissue disease; time to PSA progression; PSA50 response rate; time to initiation of any antineoplastic therapy and to first cytotoxic chemotherapy; time to first symptomatic skeletal event; PFS on next-line therapy; safety and tolerability (CTCAE v5.0); pharmacokinetics of PF-06821497 with enzalutamide; exploratory biomarkers including ctDNA burden; and patient-reported outcomes (BPI-SF, FACT-P, EQ-5D-5L, PRO-CTCAE), including time to definitive HRQoL deterioration.

Burden on patient: Moderate. The regimen consists of oral medications, which is convenient, but the Phase 3 design entails regular clinic visits for safety assessments, labs, and imaging for rPFS (typically every 8–12 weeks), serial PSA testing, and patient-reported outcome questionnaires. There are scheduled PK blood draws through at least six cycles and ctDNA sampling, adding venipuncture burden. No protocol-mandated biopsies or infusions are specified, and travel frequency should be similar to standard mCRPC monitoring with added early-cycle PK visits, resulting in a moderate overall burden.

Last updated: Oct 2025

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Daegu, Taegu-kwangyǒkshi, 41404, South Korea

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Junggu, Taejǒn-kwangyǒkshi, 35015, South Korea

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Madrid, 28040, Spain

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Madrid, 28050, Spain

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Hospital Universitario 12 de Octubre

Madrid, Madrid, Comunidad de, 28041, Spain

No email / No phone

Status: Recruiting

Fundación Instituto Valenciano de Oncología

Valencia, Valenciana, Comunitat, 46009, Spain

No email / No phone

Status: Recruiting

Södersjukhuset

Stockholm, Stockholms LÄN [se-01], 11883, Sweden

No email / No phone

Status: Recruiting

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

No email / No phone

Status: Recruiting

National Cheng Kung University Hospital

Tainan City, 704, Taiwan

No email / No phone

Status: Recruiting

National Taiwan University Hospital

Taipei, 10002, Taiwan

No email / No phone

Status: Recruiting

Taichung Veterans General Hospital

Taichung, 407, Taiwan

No email / No phone

Status: Recruiting

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

No email / No phone

Status: Recruiting

Ankara University Health Practice and Research Hospitals

Ankara, 06620, Turkey (Türkiye)

No email / No phone

Status: Recruiting

Memorial Ankara Hastanesi

Ankara, 06520, Turkey (Türkiye)

No email / No phone

Status: Recruiting

Sbü Gülhane Eğitim Ve Araştirma Hastanesi

Ankara, 06010, Turkey (Türkiye)

No email / No phone

Status: Recruiting

Koç Üniversitesi Hastanesi

Istanbul, İ̇stanbul, 34010, Turkey (Türkiye)

No email / No phone

Status: Recruiting

Marmara Universitesi Pendik Egitim Arastirma Hastanesi

Istanbul, İ̇stanbul, 34899, Turkey (Türkiye)

No email / No phone

Status: Recruiting

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi

Istanbul, İ̇stanbul, 34722, Turkey (Türkiye)

No email / No phone

Status: Recruiting

I.E.U. Medical Point Hastanesi

Izmir, İ̇zmir, 009035575, Turkey (Türkiye)

No email / No phone

Status: Recruiting

The Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

No email / No phone

Status: Recruiting

Royal Blackburn Hospital

Blackburn, Blackburn WITH Darwen, BB2 3HH, United Kingdom

No email / No phone

Status: Recruiting

Arizona Urology Specialists (AUS)-Orange Grove

Tucson, Arizona, 85741, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Scottsdale, Arizona, 85260, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Phoenix, Arizona, 85028, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Mesa, Arizona, 85206, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Mesa, Arizona, 85202, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Goodyear, Arizona, 85395, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Glendale, Arizona, 85306, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Gilbert, Arizona, 85297, United States

No email / No phone

Status: Recruiting

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224, United States

No email / No phone

Status: Recruiting

Palo Verde Hematology Oncology

Glendale, Arizona, 85304, United States

No email / No phone

Status: Recruiting

Arkansas Urology - Little Rock

Little Rock, Arkansas, 72211, United States

No email / No phone

Status: Recruiting

Highlands Oncology

Rogers, Arkansas, 72758, United States

No email / No phone

Status: Recruiting

Highlands Oncology

Fayetteville, Arkansas, 72703, United States

No email / No phone

Status: Recruiting

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

No email / No phone

Status: Recruiting

Adventist Health Physicians Network

Hidden Valley Lake, California, 95467, United States

No email / No phone

Status: Recruiting

Adventist Health Physicians Network

Napa, California, 94558, United States

No email / No phone

Status: Recruiting

Adventist Health St. Helena

St. Helena, California, 94574, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network (LACN)

Glendale, California, 91204, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network (LACN)

Anaheim, California, 92801, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network (LACN)

Fountain Valley, California, 92708, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network (LACN)

Glendale, California, 91206, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network (LACN)

Los Angeles, California, 90017, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network (LACN)

Los Angeles, California, 90067, United States

No email / No phone

Status: Recruiting

Accellacare of Duly

Lisle, Illinois, 60532, United States

No email / No phone

Status: Recruiting

Blessing Hospital

Quincy, Illinois, 62301, United States

No email / No phone

Status: Recruiting

Blessing Physician Services

Quincy, Illinois, 62301, United States

No email / No phone

Status: Recruiting

Duly Health and Care (Bone Scintigraphy)

Lisle, Illinois, 60532, United States

No email / No phone

Status: Recruiting

Duly Health and Care (CT and MRI)

Westmont, Illinois, 60559, United States

No email / No phone

Status: Recruiting

Adult & Pediatric Urology, PC

Omaha, Nebraska, 68114, United States

No email / No phone

Status: Recruiting

CHRISTUS St. Vincent Regional Cancer Center

Santa Fe, New Mexico, 87505, United States

No email / No phone

Status: Recruiting

Montefiore Medical Center - Medical Park

The Bronx, New York, 10461, United States

No email / No phone

Status: Recruiting

Salisbury VA Medical Center

Salisbury, North Carolina, 28144, United States

No email / No phone

Status: Recruiting

AUC Urologists, LLC

Myrtle Beach, South Carolina, 29572, United States

No email / No phone

Status: Recruiting

Carolina Urologic Research Center, LLC

Myrtle Beach, South Carolina, 29572, United States

No email / No phone

Status: Recruiting

Grand Strand Medical Center

Myrtle Beach, South Carolina, 29572, United States

No email / No phone

Status: Recruiting

Parkway Surgery Center

Myrtle Beach, South Carolina, 29572, United States

No email / No phone

Status: Recruiting

USA Clinical Trials

San Antonio, Texas, 78229, United States

No email / No phone

Status: Recruiting

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

No email / No phone

Status: Recruiting

Harborview Medical Center

Seattle, Washington, 98104, United States

No email / No phone

Status: Recruiting

Northwest Medical Specialties, PLLC

Puyallup, Washington, 98373, United States

No email / No phone

Status: Recruiting

Northwest Medical Specialties, PLLC

Gig Harbor, Washington, 98332, United States

No email / No phone

Status: Recruiting

Northwest Medical Specialties, PLLC

Federal Way, Washington, 98003, United States

No email / No phone

Status: Recruiting

Northwest Medical Specialties, PLLC

Bonney Lake, Washington, 98391, United States

No email / No phone

Status: Recruiting

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

No email / No phone

Status: Recruiting

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

No email / No phone

Status: Recruiting

IC La Serena Research

La Serena, Coquimbo Region, 1720430, Chile

No email / No phone

Status: Not yet recruiting

First Affiliated Hospital of China Medical University

Shenyang, 110001, China

No email / No phone

Status: Not yet recruiting

Guangzhou First People's Hospital

Guangzhou, Guangdong, 510180, China

No email / No phone

Status: Not yet recruiting

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, 80131, Italy

No email / No phone

Status: Not yet recruiting

The Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

No email / No phone

Status: Not yet recruiting

Medical Oncology Associates of San Diego

San Diego, California, 92123, United States

No email / No phone

Status: Not yet recruiting

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