A Phase 3 interventional study of PF-06821497 and Placebo in Metastatic Castration-Resistant Prostate Cancer, sponsored by Pfizer. Recruiting at 233 sites in 27 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Pfizer · Phase 3, Interventional, and Treatment
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.
Exclusion Criteria:
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:
Participants will receive PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
Drug: PF-06821497 · Drug: Enzalutamide
Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
Drug: Placebo · Drug: Enzalutamide
Oral continuous
Also known as: Mevrometostat
Oral continuous
Oral continuous
Also known as: Xtandi
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
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 Time To Pain Progression (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 5 years
Objective Response Rate (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 by BICR
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 per BICR 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
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 3 years.
Time to initiation of antineoplastic therapy.
Time from randomization to first use of new antineoplastic therapy.
Time frame: Randomization up to approximately 5 years.
Time to initiation of cytotoxic chemotherapy.
Time from randomization to first use of new cytotoxic chemotherapy.
Time frame: Randomization up to approximately 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 3 years.
Progression free survival on next line of therapy
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.
Time frame: Randomization up to approximately 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.
Time frame: Randomization up to approximately 5 years
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 3 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 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)
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 5 years
Change from baseline in BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25)
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 Week 25
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 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)
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: Randomization up to approximately 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 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 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 5 years
Showing the first 100 of 233 sites across 27 countries.
Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Pfizer