Sponsor: Pfizer (industry)
Phase: 3
Start date: Oct. 21, 2024
Planned enrollment: 600
Mervometostat (more commonly spelled mevrometostat; PF-06821497) is an investigational oral cancer drug. Human results have been reported from early-phase studies in follicular lymphoma and metastatic castration-resistant prostate cancer (mCRPC). Phase 3 prostate-cancer trials are underway; the results below do not establish a clinical benefit. (annalsofoncology.org)
Mevrometostat inhibits EZH2, an enzyme involved in repressing gene expression through methylation of histone H3. Reduced H3K27 methylation has been observed in samples from treated patients, providing evidence that the drug engages its target. (ascopubs.org)
In an 81-patient randomized phase 1 dose-expansion study of people with previously treated mCRPC, mevrometostat plus enzalutamide was compared with enzalutamide alone. Median radiographic progression-free survival was 14.3 versus 6.2 months. Among patients with measurable disease, objective responses occurred in 4/15 (26.7%) versus 2/14 (14.3%); confirmed PSA declines of at least 50% occurred in 34.1% versus 15.4%. These are preliminary findings from a small study, not phase 3 results. (meeting.neaua.org)
In an earlier phase 1 monotherapy cohort, 4 of 15 patients with follicular lymphoma had partial responses. (annalsofoncology.org)
In the randomized mCRPC study, grade 3 or higher treatment-emergent adverse events occurred in 53.7% receiving the combination and 42.5% receiving enzalutamide alone. Diarrhea was reported in 78.0% versus 15.0%, respectively; decreased appetite, altered taste, and anemia were also more frequent with the combination. No treatment-related deaths were reported. (meeting.neaua.org)
Last updated: Sep 2026
Goal: Determine whether mevrometostat plus enzalutamide improves radiographic progression-free survival compared with physician’s choice of enzalutamide or docetaxel after progression on abiraterone in metastatic castration-resistant prostate cancer (mCRPC).
Patients: Adults with metastatic prostate adenocarcinoma without small-cell features, progression on abiraterone given for metastatic castration-sensitive disease or first-line mCRPC, ECOG performance status 0–2, and life expectancy of at least 6 months. Prior enzalutamide or other next-generation androgen receptor inhibitors are excluded; prior docetaxel is permitted only in the castration-sensitive setting under specified conditions.
Design: Randomized, open-label, multicenter comparison of the combination against physician’s choice of active treatment. Radiographic outcomes are assessed by blinded independent central review.
Treatments: The investigational arm receives oral mevrometostat (PF-06821497) 875 mg twice daily plus oral enzalutamide 160 mg daily. Mevrometostat inhibits EZH2, an epigenetic enzyme involved in histone H3 methylation and gene repression. A small randomized phase 1 mCRPC study reported median radiographic progression-free survival of 14.3 months with the combination versus 6.2 months with enzalutamide alone; these preliminary findings do not establish phase 3 benefit, and diarrhea and grade ≥3 adverse events were more frequent with the combination. The comparator is physician’s choice of enzalutamide 160 mg daily, an androgen receptor inhibitor, or docetaxel 75 mg/m² intravenously every 21 days, a cytotoxic chemotherapy.
Outcomes: The primary endpoint is radiographic progression-free survival by blinded independent central review using RECIST v1.1 for soft-tissue disease and PCWG3 criteria for bone disease. Secondary measures include overall survival, objective response and response duration, PSA outcomes, subsequent therapy, symptomatic skeletal events, adverse events, patient-reported pain and quality of life, mevrometostat pharmacokinetics, and circulating tumor DNA.
Burden on patient: Moderate. Treatment requires ongoing visits, imaging, laboratory and safety assessments, and multiple patient-reported questionnaires; selected visits include pharmacokinetic blood draws through cycle 6 and circulating tumor DNA sampling. Daily oral treatment may limit travel in the combination and enzalutamide groups, whereas patients assigned docetaxel need intravenous treatment every 21 days. No mandatory biopsy or exact imaging schedule is specified.
Last updated: Sep 2026
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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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
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Homewood, Alabama, 35209, United States
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Los Angeles, California, 90067, United States
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Los Angeles, California, 90017, United States
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Glendale, California, 91206, United States
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Bonita Springs, Florida, 34135, United States
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Bradenton, Florida, 34211, United States
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Cape Coral, Florida, 33909, United States
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Fort Myers, Florida, 33905, United States
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Fort Myers, Florida, 33908, United States
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N. Venice, Florida, 34275, United States
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Naples, Florida, 34102, 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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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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Plantation, Florida, 33324, United States
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Coral Gables, Florida, 33146, United States
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Westmont, Illinois, 60559, United States
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Lisle, Illinois, 60532, 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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Cape May Court House, New Jersey, 08210, 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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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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Swansea, SA2 8QA, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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London, NW1 2PG, United Kingdom
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Blackburn, Blackburn WITH Darwen, BB2 3HH, United Kingdom
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Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom
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