A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.

Phase 3RecruitingNCT06629779

Pfizer900 enrolled

Overview

This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.

This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCRPC where no systemic anti-cancer treatments have been initiated after documentation of mCRPC with the exception of ADT (androgen deprivation therapy) and first-generation anti-androgen agents. Prior treatment with any of the ARSi's enzalutamide, darolutamide, apalutamide, or abiraterone acetate, is not permitted in any setting. Chemotherapy is permitted in the castrate sensitive setting. This study consists of a Screening Phase, Randomization, Treatment Phase, Safety Follow-up, and Long-Term Follow-up. Participants will be randomized on a 1:1 basis to receive (Arm A) PF-06821497 in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

900

Conditions

Metastatic Castration-Resistant Prostate Cancer

Interventions

PF-06821497DRUG

Oral continuous

PlaceboDRUG

Oral continuous

EnzalutamideDRUG

Oral continuous

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features. * Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan. * Progressive disease in the setting of medical or surgical castration. * ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator. Exclusion Criteria: * Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that make the participant inappropriate for the study. * Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery. * Clinically significant cardiovascular disease. * Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure. * Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy with a few exceptions. * Participants must be treatment naïve at the mCRPC stage, eg, no cytotoxic chemotherapy, radio-ligand therapy (i.e. 177Lu- PSMA-617), CDK4/6 inhibitors, 5-alpha reductase inhibitors for prostate cancer in any setting, androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment with the following exceptions: 1. Treatment with first-generation antiandrogen (ADT) agents; 2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion. * Previous administration with an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is longer). * Inadequate organ function.

Locations (241)

Outcomes

Primary Outcomes

Radiographic Progression Free Survival (rPFS)

rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or in bone per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines by BICR, or death, whichever occurs first.

Time frame: Randomization up to approximately 3 years

Secondary Outcomes

Overall survival (OS)

OS is defined as the time from the date of randomization to the date of death due to any cause.

Time frame: Randomization up to approximately 5 years

To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging TTPP

TTPP (alpha protected): assessed using time to first ≥2-point increase from baseline score on BPI-SF Item 3 (Worst Pain) observed at 2 consecutive visits or the initiation of short- or long-acting opioid use for pain

Time frame: Randomization up to approximately 3 years

Duration of Response (DoR) in measurable soft tissue disease

The DoR is defined as the time from the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause whichever occurs first.

Time frame: Randomization up to approximately 3 years.

Time to prostate specific antigen (PSA) progression.

Time from the date of randomization to the date of the first PSA progression. PSA progression is defined as a ≥25% increase in PSA with an absolute increase of ≥2 ng/mL above the nadir (or baseline for participants with no PSA decline), confirmed by a second consecutive PSA value at least 21 days later.

Time frame: Randomization up to approximately 3 years

Central Contacts

Pfizer CT.gov Call Center

CONTACT

1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Data from ClinicalTrials.gov

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