A study to investigate the investigational drug Mevrometostat (PF-06821497) in men with metastatic castration-sensitive prostate cancer who have not received novel hormonal therapy or chemotherapy for the treatment of metastatic prostate cancer (MEVPRO-3)

Résumé de l'étude

This is a global, multicenter, randomized, double-blind, placebo-controlled Phase III study to evaluate Mevrometostat in combination with Enzalutamide compared to placebo in combination with Enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC) who have not received systemic cancer therapy, except for androgen deprivation therapies (ADT) and first-generation antiandrogens. Prior therapy with up to 3 months of ADT (chemical or surgical) is allowed, without radiological evidence of disease progression or rising PSA levels prior to Day 1 indicating disease progression. Approximately 1000 participants will be randomized in a 1:1 ratio to the following arms: • Experimental Arm A: Mevrometostat 875 mg twice daily (BID) + Enzalutamide 160 mg once daily (QD) • Comparator Arm B: Placebo BID + Enzalutamide 160 mg QD Randomization will be stratified by: • Disease volume (low vs. high). High disease volume is defined by visceral metastases or at least four bone lesions, with at least one outside the vertebrae and pelvis. • De novo mCSPC vs. recurrent mCSPC Treatment with the study intervention will continue until radiological disease progression according to BICR, participant withdrawal, unacceptable toxicity, or other criteria for discontinuation of the study intervention are met. Participants will begin long-term follow-up (LTFU) after safety monitoring. If the participant has not withdrawn from study procedures and/or post-treatment follow-up, LTFU will continue until the end of the study. Participants are encouraged to continue receiving the study treatment until radiological progression is confirmed by BICR.

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Intervention étudiée

Brief summary

This study investigates whether a combination of the investigational drug Mevrometostat (PF-06821497) and Enzalutamide is more effective in participants with mCSPC who have not been pre-treated with ARPI and have not received chemotherapy in the mCSPC setting compared to Enzalutamide alone.

In the trial: Arm A

Participants will receive Mevrometostat/PF-06821497 (875 mg) BID (twice daily) + Enzalutamide 160 mg QD (once daily).

Active comparator: Arm B

Participants will receive placebo BID (twice daily) + Enzalutamide 160 mg QD (once daily).

Inclusion criteria

Male participants aged ≥ 18 years (or the minimum age for consent according to local regulations) at screening.

Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.

Metastatic prostate cancer, documented by positive bone scintigraphy (in bone disease) or metastatic lesion(s) on CT or MRI (in soft tissue/visceral disease).

Resolution of acute effects of prior therapy to a severity of ≤ 1 on CTCAE at baseline (except for AEs that the investigator deems not to pose a safety risk).

Participants must have an ECOG-PS of 0 or 1.

Exclusion criteria

Any medical or psychiatric conditions, including recent (within the last year) or active suicidal thoughts or behaviors, or laboratory abnormalities that increase the risk of study participation or may render the patient unsuitable for the study in the investigator's opinion.

Clinically significant cardiovascular disease.

Known or suspected brain metastases or active leptomeningeal disease.

Participants must not have been pre-treated in the mCSPC setting, e.g., participants must not have received cytotoxic chemotherapy, with the following exceptions:

Treatment with first-generation antiandrogens (ADT) is allowed for mCSPC.

Prior administration of an investigational product (drug or vaccine) within 30 days.

Current use or anticipated need for medications that are known strong CYP3A4/5 inhibitors and inducers (except for Enzalutamide in this study).

Inadequate organ function.

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Maladie en cours d'investigation

Prostate cancer

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Sponsor

Pfizer AG, Zürich Pfizer Inc., New York, USA

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Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)

Commission cantonale de Zurich

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Date d'approbation du comité d'éthique

05.12.2025

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Résultats de l'essai