Mevrometostat + Enzalutamide for Prostate Cancer

Recruiting at 77 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Enzalutamide

Must not be taking: Strong CYP3A4/5 inhibitors

Disqualifiers: Cardiovascular disease, Brain metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug combination can better treat metastatic castration-sensitive prostate cancer (mCSPC) compared to an existing treatment alone. Researchers aim to determine if adding mevrometostat, a potential new drug, to enzalutamide improves outcomes for men who have not yet tried certain cancer therapies. Men with confirmed prostate cancer that has spread and who haven't received chemotherapy for this type of cancer might be suitable candidates. Participants will receive either the drug combination or a placebo plus enzalutamide to evaluate which works best. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use drugs that strongly affect certain liver enzymes (CYP3A4/5 inhibitors and inducers) during the study, except for enzalutamide.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mevrometostat is generally well-tolerated. In a previous study, patients who took mevrometostat with enzalutamide experienced fewer side effects when using a lower dose of mevrometostat with food, compared to a higher dose without food. This suggests that taking the drug with food might help reduce side effects.

While specific information on severe side effects is not available, the drug's progression to later stages of clinical trials indicates it has passed earlier safety tests. This suggests that serious safety issues are unlikely at this point. For any concerns or questions about the treatment, it is advisable to consult the clinical trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Mevrometostat is unique because it targets the epigenetic regulation in cancer cells, something that most current prostate cancer treatments, like hormone therapies and chemotherapy, do not address. This drug works by inhibiting specific enzymes, potentially halting cancer cell growth more effectively. Researchers are excited about mevrometostat because it could offer a new approach to combat prostate cancer, especially for cases that are resistant to existing hormone treatments. By combining it with enzalutamide, a standard hormone therapy, there is potential for enhanced effectiveness against aggressive cancer types.

What evidence suggests that the combination of mevrometostat and enzalutamide could be effective for prostate cancer?

Research has shown that combining mevrometostat with enzalutamide can effectively treat prostate cancer. In this trial, participants in Arm A will receive this combination. Studies have found that it reduced the risk of cancer progression or death by 49% compared to enzalutamide alone, which participants in Arm B will receive with a placebo. Another study reported that this combination delayed cancer progression by an average of 8 months. These findings suggest that adding mevrometostat to enzalutamide might be more effective than using enzalutamide alone. Overall, early research indicates promising results for this combination in fighting tumors. ^{3 5 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic castration-sensitive prostate cancer (mCSPC) who haven't been treated with AR pathway inhibitors (ARPIs) or chemotherapy in the mCSPC setting. Participants should meet other specific health criteria not detailed here.

Inclusion Criteria

I am a man aged 18 or older.

My prostate cancer is confirmed without small cell features.

My prostate cancer has spread, confirmed by scans.

Exclusion Criteria

I have a serious heart condition.

I have brain metastasis or active leptomeningeal disease.

My organs are not functioning properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization

Participants are randomized to receive either mevrometostat with enzalutamide or placebo with enzalutamide

Treatment

Participants receive the assigned treatment regimen

Up to 5 years

Safety Follow-up

Participants are monitored for adverse events and safety outcomes

Up to 5 years

Long-Term Follow-up

Participants are monitored for long-term outcomes such as overall survival and progression-free survival

Up to 9 years

What Are the Treatments Tested in This Trial?

Interventions

• Mevrometostat

Trial Overview The study tests if taking mevrometostat along with enzalutamide improves outcomes compared to just enzalutamide alone in mCSPC patients. Mevrometostat is experimental, while enzalutamide is already used for prostate cancer.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

Participants will receive mevrometostat/PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)

Group II: Arm B Active Control 2 Interventions

Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Citations

1. oncologynewscentral.com oncologynewscentral.com/prostate-cancer/mevrometostat-combo-posts-strong-data-in-early-phase-prostate-cancer-trial

Mevrometostat Combo Posts Strong Data in Early-Phase ... “Mevrometostat in combination with enzalutamide showed a promising antitumor effect compared to enzalutamide alone, with a 49% reduction in the ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.LBA138

Mevrometostat (PF-06821497), an enhancer of zeste ... Results: As of Sept 2, 2024,81 pts were included (M+E, n=41; E, n=40). Median (IQR) follow-up was 9.6 (3.1-14.5) mo. Median (range) age (yrs) ...

3. onclive.com onclive.com/view/mevrometostat-plus-enzalutamide-improves-rpfs-vs-enzalutamide-in-metastatic-crpc

Mevrometostat Plus Enzalutamide Improves rPFS vs ... [vs enzalutamide alone yielded] an 8-month improvement in median rPFS or a 49% reduction in the risk of progression or death,” lead study author ...

4. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/160952-asco-2025-mevrometostat-in-combination-with-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-previously-treated-with-abiraterone-acetate-the-phase-3-randomized-mevpro-1-study.html

The Phase 3, Randomized MEVPRO-1 Study A phase 1/2 dose-expansion study (NCT03460977) evaluating mevrometostat plus enzalutamide demonstrated preliminary efficacy and a manageable ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT457778

Phase 1 trial of mevrometostat (PF-06821497), a potent ... Serious TEAEs related to M were observed in 6.4% of pts. No treatment-related deaths were observed. Conclusions: M+E shows promising activity in both post-A ( ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5046

Safety and pharmacokinetics of mevrometostat (M) in ... In pts with mCRPC treated with M + E, M 875 mg with food had an improved safety profile compared with M 1250 mg on an empty stomach.

7. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/161084-xasco-2025-safety-and-pharmacokinetics-of-mevrometostat-m-in-combination-with-enzalutamide-e-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc.html

Safety and pharmacokinetics of mevrometostat in ... The combination of mevrometostat (1250 mg twice daily on an empty stomach) and enzalutamide (160 mg once daily) demonstrated improved clinical outcomes.

8. ecancer.org ecancer.org/en/video/12299-mevrometostat-and-enzalutamide-show-improved-outcomes-compared-to-enzalutamide-alone-in-mcrpc

Mevrometostat and enzalutamide show improved ... The trial shows significant improvement in progression-free survival with the combination treatment of mevrometostat and enzalutamide.