A Study to Learn About the Investigational Medicine Called PF-06821497 (Mevrometostat) in Men With mCRPC Who Were Previously Treated With Abiraterone Acetate for Prostate Cancer (MEVPRO-1).
NCT Number: NCT06551324
Acronym: MEVPRO-1
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Interventions: DRUG: PF-06821497|DRUG: Docetaxel|DRUG: Enzalutamide
Sponsor: Pfizer
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 600
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-16
Completion Date: 2028-10-29
Locations: Baptist M&S Imaging (Medical Center), San Antonio, Texas, 78229, United States|USA Clinical Trials, San Antonio, Texas, 78229, United States

Summary:
Pfizer MEVPRO-1 (C2321014) is a randomized, open-label, multi-center clinical trial evaluating whether combining the study medicine (PF-06821497) with enzalutamide is safe and effective compared to physician's choice of either second-line androgen receptor (AR) directed therapy with enzalutamide or docetaxel (chemotherapy) for treating metastatic castration-resistant prostate cancer (mCRPC) after progression on prior abiraterone acetate treatment.

The primary objective of this clinical trial is to assess the radiographic progression free survival (rPFS) of the combination of PF-06821497 plus enzalutamide versus physician's choice of enzalutamide or docetaxel.

Primary Outcome Measures: Radiographic Progression Free Survival (rPFS) assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3), 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., Randomization up to approximately 2 years.
Secondary Outcome Measures: Overall survival (OS), OS is defined as the time from the date of randomization to the date of death due to any cause., Randomization up to approximately 4.5 years.|Objective Response (ORR), The objective response rate is defined as the proportion of participants with measurable soft tissue disease at baseline who have a confirmed objective response of complete response (CR) or partial response (PR) per RECIST v1.1., Randomization up to approximately 4.5 years.|Duration of Response (DoR) in measurable soft tissue disease, The DoR is defined as 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., Randomization up to approximately 4.5 years.|Time to prostate specific antigen (PSA) progression., Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline., Randomization up to approximately 4.5 years.|Time to initiation of antineoplastic therapy., Time from randomization to first use of new antineoplastic therapy., Randomization up to approximately 4.5 years.|Prostate Specific Antigen Response, Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline., Randomization up to approximately 4.5 years.|Incidence of Adverse Events, Type, incidence, severity \[as graded by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v5.0\], seriousness and relationship to study medications of AEs., Randomization up to approximately 4.5 years|Time to first symptomatic skeletal event, Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first)., Randomization up to approximately 4.5 years.|Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF), Analysis of Brief Pain Inventory-Short Form (BPI-SF) will be based on the pain severity score (mean of individual BPI-SF items 3, 4, 5 and 6), the pain interference score (mean of items 9A-9G), and the single BPI-SF Item 3 which asks the patient to rate pain at its worst in the last 24 hours., Randomization up to approximately 4.5 years|Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P), Change from baseline in HRQoL (FACT-P total score) will be presented. The FACT-P total score will be calculated based on the participant responses to the 39 items in the FACT-P questionnaire. Each item is rated on a 0 to 4 Likert-type scale and then combined to produce the FACT-P total score (0-156), with higher scores representing better health-related quality of life., Randomization to approximately 4.5 years|Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P), Change from baseline in social/family well-being score will be presented. The social/family well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale, Randomization up to approximately 4.5 years|Change from baseline in emotional well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P), Change from baseline in emotional well-being score will be presented. The emotional well-being score will be calculated based on 6 items in the FACT-P questionnaire; score range 0-24. Each item is rated on a 0 to 4 Likert-type scale, Randomization up to approximately 4.5 years|Change from baseline in functioning well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P), Change from baseline in functioning well-being score will be presented. The functioning well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale, Randomization up to approximately 4.5 years|Change from baseline in physical well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P), Change from baseline in physical well-being score will be presented. The physical well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale, Randomization to approximately 4.5 years|Change from baseline in symptoms per Functional Assessment of Cancer Therapy - Prostate (FACT-P), Change from baseline prostate cancer symptoms (PCS) score will be presented. The PCS score will be calculated based on 12 items in the FACT-P questionnaire; score range 0-48. Each item is rated on a 0 to 4 Likert-type scale, Randomization up to approximately 4.5 years|Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L), Participants will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 possible responses that record the level of severity (no problems, slight problems, moderate problems, severe problems, or extreme problems) within each dimension. The questionnaire also includes a visual analog scale to self-rate general health state on a scale from "the worst health you can imagine" to "the best health you can imagine.", Randomizaton up to approximately 4.5 years|Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE), Each selected PRO-CTCAE items will be assessed related to one or more attributes that include counts for the frequency, severity, and/or interference with usual or daily activities., Randomization up to approximately 4.5 years|Overall side effect burden as measured by the FACT- GP5, The FACT-GP5 question assesses overall side effect burden with the following response options "I am bothered by side effects of treatment," is rated on a 5-point scale ranging from "not at all" (0) to "very much" (4) and counts will be presented., Randomization to approximately 4.5 years|Time to confirmatory deterioration in patient-reported pain symptoms per BPI-SF Item 3 "worst pain in 24 hours", Defined as the time from randomization to onset of pain progression, which is defined as \> 2-point increase from baseline in the score from the BPI-SF Question 3 that is confirmed at the next consecutive assessment \> 4 weeks apart or an initial deterioration followed by death before the next assessment, Randomization up to approximately 4.5 years|Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P, Defined as the time from randomization to onset of definitive deterioration in FACT-P total score, which is defined as \>10 point decrease from baseline and no subsequent observations with a \<10 point decrease from baseline FACT-P total score, Randomization up to approximately 4.5 years|Time to definitive deterioration in patient-reported physical well-being per FACT-P, Time to definitive deterioration in physical well-being (PWB) per FACT-P is defined as the time from randomization to onset of definitive deterioration in physical well-being, which is defined as ≥3-point, Randomization up to approximately 4.5 years|To evaluate the PK of PF-06821497 when dosed with enzalutamide, PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits., Cycle 1 (each cycle is 28 days), Day 1 to last PK draw at the end of Cycle 6, Day 1.|To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden., Evaluation of ctDNA burden at baseline and on study., Baseline up to approximately 2 years.