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

Clinicaltrials.gov ID: NCT06629779
db-list-check Status RECRUITING
b-loader Phase PHASE3
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 900

Conditions

Metastatic Castration-Resistant Prostate Cancer

Drugs

PF-06821497, Placebo, Enzalutamide

Summary

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.

Detailed Description

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.

Locations

1 location Found with status Recruiting

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Eligibility Criteria

Inclusion Criteria:

* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* 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.
* Surgically or medically castrated, with serum testosterone ≤50 ng/dL (≤1.73 nmol/L) at screening.
* 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.
* Prior to randomization, there must be resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1.
* 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 may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease.
* Participants must be treatment naïve at the mCRPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents and. Docetaxel treatment is allowed for mCSPC.
* Previous administration with an investigational product (drug or vaccine) within 30 days.
* Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
* Major surgery or palliative localized radiation therapy within 14 days before randomization.
* Inadequate organ function.

Study Plan

Arm A

EXPERIMENTAL

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

  • DRUG:

    PF-06821497

    Description:

    Oral continuous
  • DRUG:

    Enzalutamide

    Description:

    Oral continuous

Arm B

ACTIVE_COMPARATOR

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

  • DRUG:

    Placebo

    Description:

    Oral continuous
  • DRUG:

    Enzalutamide

    Description:

    Oral continuous

Outcome Measures

Primary Outcome Measures

Radiographic Progression Free Survival (rPFS)

Time Frame: Randomization up to approximately 3 years

Secondary Outcome Measures

Overall survival (OS)

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

Time Frame: Randomization up to approximately 3 years

Duration of Response (DoR) in measurable soft tissue disease

Time Frame: Randomization up to approximately 3 years.

Time to prostate specific antigen (PSA) progression.

Time Frame: Randomization up to approximately 3 years

Prostate Specific Antigen Response

Time Frame: Randomization up to approximately 3 years.

Time to initiation of antineoplastic therapy.

Time Frame: Randomization up to approximately 3 years.

Time to initiation of cytotoxic chemotherapy.

Time Frame: Randomization up to approximately 3 years

Time to first symptomatic skeletal event

Time Frame: Randomization up to approximately 3 years.

Progression free survival on next line of therapy

Time Frame: Randomization up to approximately 3 years

Incidence of Adverse Events

Time Frame: Randomization up to approximately 5 years

To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden.

Time Frame: Baseline up to approximately 3 years.

To evaluate the PK of PF-06821497 when dosed with enzalutamide

Time Frame: Cycle 1 Day 15 to last PK draw at Cycle 6 Day 1 (cycle length is 28 days)

Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)

Time Frame: Randomization up to approximately 5 years

Change from baseline in BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25)

Time Frame: Randomization up to Week 25

Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)

Time Frame: Randomization up to approximately 5 years

Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)

Time Frame: Randomization up to approximately 5 years

Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)

Time Frame: Randomization up to approximately 5 years

Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P

Time Frame: Randomization up to approximately 5 years

Timeline

  • Last Updated
    November 20, 2024
  • Start Date
    October 8, 2024
  • Today
    February 5, 2025
  • Completion Date ( Estimated )
    November 30, 2028

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