Brief 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.
Brief Title
A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-800-718-1021
Central Contact Email
ClinicalTrials.gov_Inquiries@pfizer.com
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Castration-Resistant Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
* 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.
* Progressive disease in the setting of medical or surgical castration.
* 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 make the participant inappropriate for the study.
* Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure.
* Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy with a few exceptions.
* 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:
1. Treatment with first-generation antiandrogen (ADT) agents;
2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion.
* Previous administration with an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is longer).
* Inadequate organ function.
* 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.
* Progressive disease in the setting of medical or surgical castration.
* 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 make the participant inappropriate for the study.
* Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure.
* Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy with a few exceptions.
* 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:
1. Treatment with first-generation antiandrogen (ADT) agents;
2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion.
* Previous administration with an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is longer).
* Inadequate organ function.
Inclusion Criteria
Inclusion Criteria:
* 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.
* Progressive disease in the setting of medical or surgical castration.
* ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator.
* 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.
* Progressive disease in the setting of medical or surgical castration.
* ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator.
Gender
Male
Gender Based
false
Keywords
MEVROMETOSTAT
METASTATIC CASTRATION RESISTANT PROSTATE CANCER
PF-06821497
EZH2
enhancer of zeste homologue-2
enzalutamide
mCRPC
Prostrate Cancer
castrate resistant prostate cancer
prostatecancer-study.com
efficacy
safety
pharmacokinetics
pharmacodynamics
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06629779
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
C2321003
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF PF-06821497 (MEVROMETOSTAT) WITH ENZALUTAMIDE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MEVPRO-2)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Radiographic Progression Free Survival (rPFS)
Outcome Time Frame
Randomization up to approximately 3 years
Secondary Ids
Secondary Id
2024-511652-40-00
Secondary Outcomes
Outcome Description
OS is defined as the time from the date of randomization to the date of death due to any cause.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Overall survival (OS)
Outcome Description
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
Outcome Time Frame
Randomization up to approximately 3 years
Outcome Measure
To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging TTPP
Outcome Description
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 or death due to any cause whichever occurs first.
Outcome Time Frame
Randomization up to approximately 3 years.
Outcome Measure
Duration of Response (DoR) in measurable soft tissue disease
Outcome Description
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.
Outcome Time Frame
Randomization up to approximately 3 years
Outcome Measure
Time to prostate specific antigen (PSA) progression.
Outcome Description
Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline.
Outcome Time Frame
Randomization up to approximately 3 years.
Outcome Measure
Prostate Specific Antigen Response
Outcome Description
Time from randomization to first use of new antineoplastic therapy.
Outcome Time Frame
Randomization up to approximately 3 years.
Outcome Measure
Time to initiation of antineoplastic therapy.
Outcome Description
Time from randomization to first use of new cytotoxic chemotherapy.
Outcome Time Frame
Randomization up to approximately 3 years
Outcome Measure
Time to initiation of cytotoxic chemotherapy.
Outcome Description
Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first).
Outcome Time Frame
Randomization up to approximately 3 years.
Outcome Measure
Time to first symptomatic skeletal event
Outcome Description
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.
Outcome Time Frame
Randomization up to approximately 3 years
Outcome Measure
Progression free survival on next line of therapy
Outcome Description
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.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Incidence of Adverse Events
Outcome Description
Evaluation of ctDNA burden at baseline and on study.
Outcome Time Frame
Baseline up to approximately 3 years.
Outcome Measure
To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden.
Outcome Description
PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits
Outcome Time Frame
Cycle 1 Day 15 to last PK draw at Cycle 6 Day 1 (cycle length is 28 days)
Outcome Measure
To evaluate the PK of PF-06821497 when dosed with enzalutamide
Outcome Description
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.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)
Outcome Description
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.
Outcome Time Frame
Randomization up to Week 25
Outcome Measure
Change from baseline in BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25)
Outcome Description
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.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Outcome Description
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."
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)
Outcome Description
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.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)
Outcome Description
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
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404