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

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.

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

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

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 by BICR

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 per BICR or death due to any cause whichever occurs first.

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.

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

Time from randomization to first use of new antineoplastic therapy.

Time from randomization to first use of new cytotoxic chemotherapy.

Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first).

the time from the date of randomization to the first occurrence of investigator-determined disease progression (PSA progression, progression on imaging, or clinical progression) or death due to any cause, whichever occurs first, while the participant was receiving first subsequent therapy for prostate cancer.

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.

Evaluation of ctDNA burden at baseline and on study.

PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits

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.

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.

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.

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."

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.

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.

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