Mevrometostat + Enzalutamide for Prostate Cancer

Recruiting at 283 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Enzalutamide

Must not be taking: 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 3 years

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug, PF-06821497 (Mevrometostat), combined with enzalutamide, can more effectively treat prostate cancer that has spread beyond the prostate compared to enzalutamide alone. It specifically targets patients whose cancer has become resistant to standard hormone treatments but who have not yet received certain other prostate cancer therapies. Ideal candidates have confirmed prostate cancer that has spread to bones or soft tissue and whose disease progresses despite treatments that lower testosterone levels. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients 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 taking your current medications, but you cannot use drugs that strongly affect certain liver enzymes (CYP3A4/5) 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 the combination of mevrometostat (PF-06821497) and enzalutamide is generally well-tolerated by patients with advanced prostate cancer that no longer responds to hormone therapy. One study found that taking 875 mg of mevrometostat twice a day with food resulted in fewer side effects compared to a higher dose taken without food.

While enzalutamide alone is known to be safe for treating prostate cancer, combining it with mevrometostat did not lead to more severe side effects. Earlier research indicates that this combination appears safe for many people, with manageable side effects. ^{1 2 3 4 5}

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

Researchers are excited about Mevrometostat combined with enzalutamide for prostate cancer because this combination targets the disease in a novel way. Unlike standard hormonal therapies that primarily block androgen receptors, Mevrometostat, the study drug, inhibits a specific enzyme involved in cancer cell growth. This new mechanism of action could potentially enhance the effectiveness of enzalutamide, a widely used treatment, by tackling cancer cells more aggressively. The hope is that this combination could offer improved outcomes for patients compared to existing treatments like enzalutamide alone.

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

In this trial, participants in Arm A will receive a combination of mevrometostat (PF-06821497) and enzalutamide. Research suggests this combination may effectively treat prostate cancer. Studies found that it reduced the risk of cancer progression or death by 49% compared to enzalutamide alone. Additionally, it extended the time patients lived without cancer worsening by 8 months. These findings indicate that adding mevrometostat to enzalutamide could offer a better treatment option for advanced prostate cancer that no longer responds to standard hormone therapy. Participants in Arm B will receive a placebo alongside enzalutamide. ^{4 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 men with metastatic castration-resistant prostate cancer (mCRPC) who haven't previously been treated with ARSi or abiraterone. Participants should meet other study requirements to join.

Inclusion Criteria

My cancer has worsened despite hormone therapy or surgery.

My prostate cancer is confirmed without small cell features.

My side effects from previous treatments have mostly gone away.

Exclusion Criteria

Any medical 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

Previous administration with an investigational product (drug or vaccine) within 30 days

I have not received chemotherapy for my metastatic castration-resistant prostate cancer, except for first-generation antiandrogens or Docetaxel for metastatic castration-sensitive prostate cancer.

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 PF-06821497 with enzalutamide or placebo with enzalutamide

Treatment

Participants receive either PF-06821497 in combination with enzalutamide or placebo in combination with enzalutamide

Up to 3 years

Safety Follow-up

Participants are monitored for safety and adverse events

Up to 5 years

Long-Term Follow-up

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

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• PF-06821497

Trial Overview

The study tests if PF-06821497 combined with enzalutamide is more effective than enzalutamide alone in treating mCRPC. Some participants will receive a placebo instead of PF-06821497.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

Participants will receive 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

Published Research Related to This Trial

Enzalutamide has been proven effective in increasing overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously undergone docetaxel chemotherapy, as demonstrated in the AFFIRM study.

The drug is generally well tolerated by patients, and ongoing trials, such as the PREVAIL study, are exploring its effectiveness in earlier treatment stages before chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of enzalutamide, a new hormonal therapy]. Beuzeboc, P., Benderra, MA., de La Motte Rouge, T.[2021]

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]

In a real-world study involving 1732 men with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide demonstrated a median time to treatment failure of 12.9 months for patients who had not previously received chemotherapy or abiraterone, compared to 8.4 months for those who had, indicating its efficacy in different treatment settings.

The safety profile of enzalutamide was consistent with previous clinical trials, with treatment-emergent adverse events reported in 51.0% of chemotherapy-naïve patients and 62.2% of post-chemotherapy patients, with fatigue being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE. Payne, H., Robinson, A., Rappe, B., et al.[2022]

In a phase 2 study involving 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Tombal, B., Borre, M., Rathenborg, P., 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]

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]

In the PREVAIL study involving 872 men with metastatic castration-resistant prostate cancer, significant declines in prostate-specific antigen (PSA) levels after 3 months of enzalutamide treatment were linked to improved overall survival and progression-free survival outcomes.

Specifically, 88% of patients experienced a PSA decline of at least 30%, and greater declines were associated with longer survival and better quality of life, indicating that monitoring PSA levels can provide valuable prognostic information for treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial. Armstrong, AJ., Lin, P., Higano, CS., et al.[2021]

Enzalutamide significantly improves overall survival in men with metastatic, castration-resistant prostate cancer (mCRPC), showing a 37% reduced risk of death compared to placebo, with median survival times of 18.4 months versus 13.6 months.

The results from the phase III AFFIRM trial support the continued targeting of the androgen receptor as an effective treatment strategy for prostate cancer, even after patients have developed resistance to castration therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. Aragon-Ching, JB.[2021]

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]

Enzalutamide is an effective and well-tolerated treatment for Italian patients with hormone-refractory metastatic castration-resistant prostate cancer who have progressed after chemotherapy, as demonstrated in a study of 60 patients.

The treatment led to a significant reduction in serum prostate-specific antigen (PSA) levels, which correlated with improved overall survival, indicating that PSA levels can be a predictive marker for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Efficacy of Enzalutamide in Metastatic Prostate Cancer: Prospective Single-center Study. Cicero, G., DE Luca, R., Dorangricchia, P., 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]

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 a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

Citations

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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) ...

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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 ( ...

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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 ...

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This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as a single ...

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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.

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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.

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This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in ...