PF-06821497 + Enzalutamide for Prostate Cancer

(MEVPRO-1 Trial)

Recruiting at 285 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: Chemotherapy, ARSi, PARP, others

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 approximately 2 years

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment combination for individuals with prostate cancer that has spread and is unresponsive to current treatments. The study tests whether adding a new drug, PF-06821497 (Mevrometostat), to the existing drug enzalutamide is more effective than standard treatments like enzalutamide or the chemotherapy drug docetaxel. It targets those whose prostate cancer has spread to bones or soft tissue and who have not responded to abiraterone acetate. Participants should not have received certain other cancer treatments or have specific health conditions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity 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 taking your current medications, but you cannot have had certain prostate cancer treatments like enzalutamide or chemotherapy before. You should discuss your current medications with the trial team to see if they are allowed.

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

Research has shown that using PF-06821497 with enzalutamide is generally safe. Studies have tested various doses of these drugs and found that patients usually tolerate them well. One study, in particular, used doses similar to those in this trial and found that the combination benefited patients with advanced prostate cancer. Although all treatments can have side effects, these results suggest that PF-06821497 with enzalutamide has been reasonably safe for patients in past studies. ^{1 2 3 4 5}

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

Researchers are excited about PF-06821497 in combination with enzalutamide for treating prostate cancer because it introduces a new mechanism of action. While most existing treatments, like enzalutamide and docetaxel, focus on hormone therapy or chemotherapy, PF-06821497 is designed to inhibit a specific enzyme involved in cancer cell growth. This unique approach could potentially enhance the effectiveness of enzalutamide, offering a promising new option for patients who may not respond well to current therapies. By targeting cancer cells in a different way, this combination aims to improve outcomes and provide a more effective treatment strategy for prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that using PF-06821497 with enzalutamide, as studied in Arm A of this trial, may be promising for treating advanced prostate cancer that no longer responds to hormone therapy. Studies have found that this combination can lower the risk of cancer worsening or death by 49% compared to enzalutamide alone. Additionally, patients taking both medications lived about 8 months longer without their cancer progressing. These results suggest that PF-06821497, when combined with enzalutamide, might be more effective than current treatments like enzalutamide alone or chemotherapy with docetaxel, which are options in Arm B of this trial. ^{1 3 4 6 7}

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 men with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with Abiraterone Acetate. Participants should not have received certain other treatments and must meet specific health criteria.

Inclusion Criteria

I am castrated with low testosterone levels.

I can care for myself and my doctor believes I have at least 6 months to live.

My prostate cancer is confirmed without being a small cell type.

Exclusion Criteria

I have liver problems.

Any medical (including active or clinically significant bacterial, fungal or viral infection) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-06821497 in combination with enzalutamide or physician's choice of enzalutamide or docetaxel

Up to approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to approximately 4.5 years

What Are the Treatments Tested in This Trial?

Interventions

• PF-06821497

Trial Overview The study is testing the safety and effectiveness of a new medicine, PF-06821497, combined with Enzalutamide compared to the standard treatment choice of either Enzalutamide alone or Docetaxel chemotherapy in treating mCRPC after prior treatment failure.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

Investigational Arm A: PF-06821497 875 mg twice daily (BID) + enzalutamide 160 mg every day (QD)

Group II: Arm B Active Control 2 Interventions

Comparator Arm B: Physician's choice of enzalutamide 160 mg QD or docetaxel 75 mg/m2 intravenous (IV) every 21 days

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

Published Research Related to This Trial

Enzalutamide significantly improves survival and delays skeletal-related events in patients with metastatic castration-resistant prostate cancer (mCRPC), as shown in the phase III AFFIRM study with consistent benefits across all subgroups.

In the phase III PREVAIL study, enzalutamide reduced the risk of radiographic progression and death in chemotherapy-naïve mCRPC patients, while also demonstrating a favorable safety profile with similar adverse event rates compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. Merseburger, AS., Haas, GP., von Klot, CA.[2020]

In a phase 3 trial involving 1199 men with castration-resistant prostate cancer, enzalutamide significantly improved overall survival compared to placebo, with a median survival of 18.4 months versus 13.6 months.

Enzalutamide also showed superior efficacy in secondary outcomes, including a 54% reduction in PSA levels and improved quality of life, although it was associated with higher rates of fatigue and other side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival with enzalutamide in prostate cancer after chemotherapy. Scher, HI., Fizazi, K., Saad, F., et al.[2022]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

The KEYNOTE-641 study is a Phase III clinical trial designed to evaluate the safety and efficacy of combining the PD-1 inhibitor pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC).

This trial aims to determine if the combination therapy can improve outcomes compared to enzalutamide alone, addressing the need for more effective treatments in a patient population with a median survival of about 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. Graff, JN., Liang, LW., Kim, J., et al.[2021]

In the final analysis of the PREVAIL study, enzalutamide significantly improved overall survival in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), reducing the hazard of death by 17% compared to placebo, with a median overall survival of 36 months versus 31 months.

However, there was a slightly higher incidence of fatal treatment-emergent adverse events with enzalutamide, including an increase in fatal cardiovascular events (1.6% vs 0.4%), indicating a need to balance survival benefits with potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial. Armstrong, AJ., Lin, P., Tombal, B., et al.[2021]

Enzalutamide is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC), approved for use both after chemotherapy and before chemotherapy, significantly improving patient survival.

The STRIVE Phase II clinical trial demonstrated that enzalutamide outperforms bicalutamide in patients with nonmetastatic and mCRPC who have not responded to androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of enzalutamide on the treatment of prostate cancer. Nadal, R., Bellmunt, J.[2021]

In a long-term study of 67 patients with hormone-naïve prostate cancer, enzalutamide monotherapy resulted in a 100% prostate-specific antigen (PSA) response rate at 97 weeks for those who remained on treatment, indicating its strong efficacy.

The treatment was well-tolerated with minimal negative effects on total-body bone mineral density, although common side effects included gynecomastia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

Citations

1. 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) ...

2. 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 ...

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

Phase 1 trial of mevrometostat (PF-06821497), a potent ... Results: As of November 2, 2023, 47 pts had received ≥1 dose of study treatment. Median (interquartile range) duration of follow up was 9.7 (2.0-22.8) months ( ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06629779

NCT06629779 | A Study to Learn How PF-06821497 ... This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination ...

6. 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.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06629779

NCT06629779 | A Study to Learn How PF-06821497 ... This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in ...