A Study of Mevrometostat With Enzalutamide in People With Prostate Cancer Who Have Previously Received Androgen Receptor Pathway Inhibitor Therapy

NCT07592910 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: c25-392
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to find out whether mevrometostat in combination with enzalutamide delays cancer progression in people with metastatic castration-resistant prostate cancer (mCRPC) who have previously received enzalutamide, darolutamide, or apalutamide in the metastatic castration-sensitive prostate cancer (mCSPC) or non-metastatic castration-resistant prostate cancer (nmCRPC) setting but have not previously progressed on abiraterone.

Conditions

Prostate Cancer (Adenocarcinoma); Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Keywords

Mevrometostat; EZH2 inhibitor; Enzalutamide; ARPI resistance; MOMENT; mCRPC; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Radiographic progression free survival (rPFS)

  rPFS by RECIST v1.1 and PCWG3 defined as time from start of study treatment to the earlier of first documentation of objective progressive disease by RECIST v1.1 or PCWG3 or death due to any cause.

  From treatment initiation until documented disease progression, death, lost to follow-up, withdrawal, administrative censoring at the time of final analysis, whichever comes first, assessed up to 24 months.

Secondary Outcomes (4)

• Overall Survival (OS)

  From start of study treatment until death from any cause, assessed up to 24 months.

• Proportion of Participants Achieving 50% Decline in PSA (PSA50 Response)

  From initiation of study treatment through study completion, assessed up to 24 months.

• Time to PSA Progression as Defined by PCWG3

  From start of study treatment until documented PSA progression, assessed up to 24 months.

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  From start of study treatment through 28 days after last dose of study drug, assessed up to 24 months.

Study Arms (1)

Mevrometostat + Enzalutamide

EXPERIMENTAL

Mevrometostat 875 mg orally twice daily (BID) with food in combination with enzalutamide 160 mg orally once daily. Treatment continues until confirmed radiographic disease progression, unacceptable toxicity, or other protocol-defined discontinuation criteria.

Drug: Mevrometostat; Drug: Enzalutamide

Interventions

Mevrometostat DRUG

875 mg oral tablet, taken twice daily with food

Also known as: PF-06821497

Mevrometostat + Enzalutamide

Enzalutamide DRUG

160 mg oral capsule, taken once daily

Also known as: Xtandi

Mevrometostat + Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Age 18 years or older
• Diagnosis of prostate cancer (adenocarcinoma) confirmed by tissue sample, without neuroendocrine or small cell features
• Currently taking or recently treated with enzalutamide, darolutamide, or apalutamide (within 30 days of screening) and willing to switch to or restart enzalutamide for this study
• Cancer has spread to bone or soft tissue (metastatic disease), confirmed by imaging
• ECOG performance status of 0, 1, or 2 (able to care for self and up and about more than 50% of waking hours)
• Testosterone level less than 50 ng/dL at screening, with ongoing hormone deprivation therapy or prior surgical castration
• If receiving bone-protective therapy (e.g., denosumab or bisphosphonates), must be on a stable dose for at least 4 weeks
• Evidence of cancer progression while on enzalutamide, darolutamide, or apalutamide, shown by rising PSA, worsening disease on imaging, or new bone lesions
• Adequate organ function based on blood tests within 28 days of starting treatment, including adequate blood counts, kidney function, and liver function
• Willing to use acceptable birth control during the study and for 30 days after the last dose

You may not qualify if:

• History of myelodysplastic syndrome, acute myeloid leukemia, or other prior cancer (exceptions: non-melanoma skin cancer, carcinoma in situ, cancers more than 3 years ago with no recurrence, or early-stage cancers with low risk of recurrence)
• Any medical or psychiatric condition, including active infection or recent suicidal ideation, that may make study participation unsafe
• History of seizure or conditions that may increase seizure risk (e.g., prior stroke, significant brain trauma), or loss of consciousness or transient ischemic attack within 12 months
• Untreated brain metastases, spinal cord compression, or clinically significant epidural disease
• Use of 5-alpha reductase inhibitors, herbal medications, or supplements known to alter PSA levels within 4 weeks of starting treatment
• AIDS-related illness or active hepatitis B or C (well-controlled HIV is allowed)
• Known history of chronic liver disease (e.g., alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, Wilson's disease, hemochromatosis)
• Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or prior gastric resection or lap-band surgery
• Clinically significant cardiovascular disease within the past 6 months (e.g., heart attack, unstable angina, stroke, heart failure NYHA Class III/IV, pulmonary embolism, significant arrhythmias), cardiac pacemaker, or QTcF greater than 480 msec on screening ECG
• Prior or current use of PARP inhibitors and/or AKT inhibitors
• Prior cancer progression on abiraterone (stopping abiraterone due to side effects is allowed)
• Known allergy to any study drug
• Blood transfusion within 28 days prior to screening blood tests
• Use of another investigational drug within 4 weeks before starting study treatment
• Any other condition that, in the opinion of the investigator, would prevent safe participation

Sponsors & Collaborators

• Prostate Cancer Clinical Trials Consortium: lead
• Pfizer: collaborator
• Dana-Farber Cancer Institute: collaborator
• Fred Hutchinson Cancer Center: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma

Interventions

PF06821497; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Michael Schweizer, MD

  University of Washington- Fred Hutch Cancer Center

  PRINCIPAL INVESTIGATOR

• Atish Choudhury, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Wise

CONTACT

215-380-9051; wises@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: May 18, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF