Sponsor: Pfizer (industry)
Phase: 3
Start date: Oct. 21, 2024
Planned enrollment: 600
Mervometostat (also spelled Mevrometostat; development code PF-06821497) is an oral, selective inhibitor of the histone methyltransferase EZH2 under clinical evaluation, most prominently in metastatic castration‑resistant prostate cancer (mCRPC), including randomized dose‑expansion data and an ongoing phase 3 trial in combination with enzalutamide. Preclinical chemistry and target engagement for PF‑06821497 have been published, and multiple ASCO meeting abstracts have reported early clinical efficacy and safety signals. (pubs.acs.org)
Note: The foundational phase 1/2 program (NCT03460977) also included follicular lymphoma and small‑cell lung cancer cohorts; public efficacy details to date are concentrated in the mCRPC combination setting. (ascopubs.org)
ClinicalTrials.gov identifier for the foundational study: NCT03460977. (pfizeroncologydevelopment.com)
Last updated: Oct 2025
Goal: Evaluate whether adding the EZH2 inhibitor mervometostat (PF-06821497) to enzalutamide improves radiographic progression-free survival compared with physician’s choice of enzalutamide or docetaxel in mCRPC after progression on abiraterone.
Patients: Adults with histologically or cytologically confirmed prostatic adenocarcinoma (no small cell features) and metastatic disease (bone and/or soft tissue) who have progressed in the castration setting after abiraterone in mCSPC or first-line mCRPC. ECOG 0–2 and life expectancy ≥6 months required. Key exclusions include prior ARSi beyond first-generation antiandrogens, prior PARP monotherapy, prior chemotherapy for prostate cancer except docetaxel in mCSPC without progression during or ≤3 months after completion, prior radioligand therapy, active CNS disease or seizures, significant cardiovascular disease, active inflammatory GI disease, and inadequate organ function.
Design: Phase 3, randomized, open-label, multicenter study enrolling approximately 600 participants. Allocation is randomized between the investigational combination and physician’s choice control. Primary purpose is treatment, with blinded independent central review for radiographic endpoints.
Treatments: Arm A: Mervometostat (PF-06821497) 875 mg orally twice daily plus enzalutamide 160 mg once daily. Mervometostat is a potent, selective EZH2 inhibitor that reduces H3K27 methylation and reactivates silenced genes, targeting PRC2-mediated epigenetic repression; it shows marked selectivity for EZH2 over EZH1. Early-phase studies in mCRPC, including combination with enzalutamide, demonstrated manageable safety, a median rPFS of approximately 17 months, and objective responses in measurable disease, supporting Phase 3 evaluation. Arm B: Physician’s choice of enzalutamide 160 mg once daily or docetaxel 75 mg/m2 IV every 21 days, both standard-of-care options post-abiraterone in mCRPC.
Outcomes: Primary: Radiographic progression-free survival by BICR per RECIST v1.1/PCWG3 or death. Key secondary endpoints include overall survival; objective response rate and duration of response in measurable soft tissue disease; PSA outcomes (time to PSA progression and PSA50 response); time to initiation of subsequent antineoplastic therapy; time to first symptomatic skeletal event; safety and tolerability (CTCAE v5.0); patient-reported outcomes including pain (BPI-SF), HRQoL (FACT-P total and domain scores), EQ-5D-5L, PRO-CTCAE, and FACT-GP5; time to definitive/confirmatory deterioration in pain and HRQoL; pharmacokinetics of PF-06821497 with enzalutamide; and ctDNA burden at baseline and on treatment.
Burden on patient: Moderate. Both arms require ongoing androgen deprivation and standard imaging for rPFS assessment similar to usual mCRPC practice. The investigational arm adds twice-daily oral mervometostat and scheduled pharmacokinetic blood draws through at least cycle 6, increasing visit time and venipuncture frequency. All participants undergo periodic CT/MRI, bone scans, PSA assessments, safety labs, and comprehensive PRO questionnaires throughout follow-up, plus optional or protocol-specified ctDNA sampling. Patients randomized to docetaxel have added infusion visits every 3 weeks and chemotherapy-related monitoring, which increases travel and clinic time compared with oral therapy. Overall procedures are consistent with a phase 3 oncology trial, with added PK and PRO schedules and, for some, IV chemotherapy contributing to the moderate burden.
Last updated: Oct 2025
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 surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line mCRPC setting is required.
* Eastern Cooperate Oncology Group (ECOG) performance status 0 - 2, with life expectancy of at least 6 months as assessed by the investigator.
Exclusion Criteria:
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may make the participant inappropriate for the study.
* Know history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure.
* Prior treatment for prostate cancer at any stage with any cytotoxic chemotherapy, radioligand therapy (i.e. 177Lu-PSMA-617, radium 223), androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment, with the following exceptions:
1. Treatment with first-generation antiandrogen agents, if discontinued prior to first dose of study intervention.
2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion.
* Previous administration with an investigational product within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is shorter).
* Inadequate organ function.
Buenos Aires, C1419AHN, Argentina
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Manresa, 8423, Spain
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London, London, CITY of, NW1 2PG, United Kingdom
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Homewood, Alabama, 35209, United States
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Tucson, Arizona, 85741, United States
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Scottsdale, Arizona, 85260, United States
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Phoenix, Arizona, 85028, United States
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Chandler, Arizona, 85224, United States
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Glendale, Arizona, 85306, United States
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Los Angeles, California, 90067, United States
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Fountain Valley, California, 92708, United States
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Palo Alto, California, 94305, United States
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Stanford, California, 94305, United States
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Santa Rosa, California, 95403, United States
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San Mateo, California, 94402, United States
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Lakewood, Colorado, 80228, United States
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Orlando, Florida, 32804, United States
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Orlando, Florida, 32804, United States
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Sarasota, Florida, 34236, United States
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Port Charlotte, Florida, 33980, United States
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Naples, Florida, 34102, United States
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Fort Myers, Florida, 33908, United States
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Cape Coral, Florida, 33909, United States
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Bradenton, Florida, 34211, United States
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Bonita Springs, Florida, 34135, United States
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Doral, Florida, 33166, United States
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Miami, Florida, 33136, United States
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Aventura, Florida, 33180, United States
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Deerfield Beach, Florida, 33442, United States
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Miami, Florida, 33136, United States
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Kendall, Florida, 33176, United States
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Plantation, Florida, 33324, United States
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Coral Gables, Florida, 33146, United States
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Lisle, Illinois, 60532, United States
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Hinsdale, Illinois, 60521, United States
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Westmont, Illinois, 60559, United States
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Lisle, Illinois, 60532, United States
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Louisville, Kentucky, 40202, United States
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Louisville, Kentucky, 40202, United States
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Louisville, Kentucky, 40245, United States
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Topsham, Maine, 04086, United States
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Westbrook, Maine, 04092, United States
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St Louis, Missouri, 63106, United States
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Egg Harbor, New Jersey, 08234, United States
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Middletown, New York, 10941, United States
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Middletown, New York, 10941, United States
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Monroe, New York, 10950, United States
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The Bronx, New York, 10468, United States
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Salisbury, North Carolina, 28144, United States
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Lancaster, Pennsylvania, 17604, United States
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Myrtle Beach, South Carolina, 29572, United States
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Myrtle Beach, South Carolina, 29572, United States
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Myrtle Beach, South Carolina, 29572, United States
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Myrtle Beach, South Carolina, 29572, United States
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Nashville, Tennessee, 37203, United States
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San Antonio, Texas, 78229, United States
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Salt Lake City, Utah, 84112, United States
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Seattle, Washington, 98109, United States
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Seattle, Washington, 98104, United States
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Seattle, Washington, 98195, United States
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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
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Baytown, Texas, 77521, United States
No email / No phone
Status: Not yet recruiting
Houston, Texas, 77058, United States
No email / No phone
Status: Not yet recruiting
Cypress, Texas, 77429, United States
No email / No phone
Status: Not yet recruiting
Houston, Texas, 77030, United States
No email / No phone
Status: Not yet recruiting
Houston, Texas, 77030, United States
No email / No phone
Status: Not yet recruiting
Sugar Land, Texas, 77479, United States
No email / No phone
Status: Not yet recruiting
The Woodlands, Texas, 77385, United States
No email / No phone
Status: Not yet recruiting
Houston, Texas, 77094, United States
No email / No phone
Status: Not yet recruiting
Houston, Texas, 77070, United States
No email / No phone
Status: Not yet recruiting