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).

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 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.

Time frame: Randomization up to approximately 2 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.

Time frame: Randomization up to approximately 2 years.

Time to prostate specific antigen (PSA) progression.

Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline.

Time frame: Randomization up to approximately 2 years.

Time to initiation of antineoplastic therapy.

Time from randomization to first use of new antineoplastic therapy.

Time frame: 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.

Time frame: Randomization up to approximately 2 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.

Time frame: 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).

Time frame: Randomization up to approximately 2 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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."

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to approximately 2 years.