Brief Summary
This study will explore whether a combination of the investigational drug mevrometostat (PF-06821497) and enzalutamide will work better than taking enzalutamide alone in participants with mCSPC who are ARPI naïve and have not yet received chemotherapy in the mCSPC setting.
Brief Title
This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve.
Detailed Description
This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating mevrometostat in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCSPC who have not received systemic anticancer treatments with the exception of androgen-deprivation therapy (ADT) and first-generation antiandrogen agents. Prior therapy with up to 3 months of ADT (chemical or surgical) is allowed, with no radiographic evidence of disease progression or rising PSA levels prior to Day 1.
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) mevrometostat (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) mevrometostat (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 Sensitive Prostate Cancer (mCSPC)
Hormone Sensitive Prostate Cancer
Prostate Cancer
Cancer of the Prostate
Eligibility Criteria
Inclusion Criteria
* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
* Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
* Participants must have ECOG PS 0 or 1.
Exclusion Criteria
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease.
* Participants must be treatment naïve at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC.
* Previous administration with an investigational product (drug or vaccine) within 30 days.
* Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
* Inadequate organ function.
* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
* Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
* Participants must have ECOG PS 0 or 1.
Exclusion Criteria
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease.
* Participants must be treatment naïve at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC.
* Previous administration with an investigational product (drug or vaccine) within 30 days.
* Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
* Inadequate organ function.
Inclusion Criteria
Inclusion Criteria
* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
* Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
* Participants must have ECOG PS 0 or 1.
* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
* Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
* Participants must have ECOG PS 0 or 1.
Gender
Male
Gender Based
false
Keywords
Hormone Sensitive Prostate Cancer
Mevrometostat
Metastatic castration sensitive prostate cancer
PF-06821497
EZH2
enhancer of zeste homologue-2
enzalutamide
mCSPC
HSPC
Prostate cancer
castrate sensitive prostate cancer
prostatecancer-study.com
Phase 3
efficacy
safety
pharmacokinetics
pharmacodynamics
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07028853
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
C2321008
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 Mevrometostat (PF-06821497) With Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer (MEVPRO-3)
Primary Outcomes
Outcome Description
rPFS is defined as the time from randomization until PD based on BICR assessment per RECIST v1.1 (soft tissue disease) and PCWG3 (bone disease), or death due to any cause, whichever occurs first.
Outcome Measure
Radiographic Progression Free Survival (rPFS)
Outcome Time Frame
Randomization up to approximately 4 years
Secondary Ids
Secondary Id
MEVPRO-3
Secondary Id
2024-519369-24-00
Secondary Outcomes
Outcome Description
OS defined as the time from the date of randomization until the date of death due to any cause.
Outcome Time Frame
Randomization up to approximately 9 years
Outcome Measure
Overall survival (OS)
Outcome Description
The proportion of participants with measurable soft tissue disease at baseline who have a confirmed objective response of CR or PR per RECIST v1.1 will be summarized along with the 95% CI.
Outcome Time Frame
Randomization up to approximately 4 years
Outcome Measure
Objective response in measurable soft tissue disease
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 4 years
Outcome Measure
Duration of Response (DoR) in measurable soft tissue disease
Outcome Description
The proportion of participants with a 50% decline from baseline in PSA that is confirmed by a second consecutive value at least 21 days later in participants with detectable PSA values at baseline will be calculated for each treatment arm.
Outcome Time Frame
Randomization up to approximately 4 years
Outcome Measure
Prostate Specific Antigen Response
Outcome Description
Time from the date of randomization to the date of the first PSA progression.
Outcome Time Frame
Randomization up to approximately 4 years
Outcome Measure
Time to prostate specific antigen (PSA) progression
Outcome Description
Time from randomization to first use of new antineoplastic therapy for prostate cancer.
Outcome Time Frame
Randomization up to approximately 4 years
Outcome Measure
Time to initiation of antineoplastic therapy
Outcome Description
Time from randomization to first tumor-related symptomatic bone fracture, surgery or radiotherapy to the bone, and spinal cord compression, whichever occurs first.
Outcome Time Frame
Randomization up to approximately 4 years
Outcome Measure
Time to first symptomatic skeletal event
Outcome Description
Time from randomization to the first date of CRPC event.
Outcome Time Frame
Randomization up to approximately 4 years
Outcome Measure
Time from randomization to CRPC
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
PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits.
Outcome Time Frame
Cycle 3 Day 1 to last PK draw at Cycle 5 Day 1 (cycle length is 28 days)
Outcome Measure
To evaluate the PK of mevrometostat when dosed in combination 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.
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
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.
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
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
Outcome Description
Change from baseline and time to definitive deterioration in participant-reported prostate cancer specific functioning, and symptoms per EORTC QLQ-PR25
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Patient-reported outcomes in cancer specific symptoms - time to definitive deterioration
Outcome Description
Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms (fatigue severity and fatigue interference) as per BFI.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms per BFI
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.
Outcome Time Frame
Randomization up to approximately 5 years
Outcome Measure
Change from baseline in participant-reported general health status per EQ-5D-5L
Outcome Description
Evaluation of ctDNA burden at baseline and on study.
Outcome Time Frame
Baseline up to approximately 4 years
Outcome Measure
To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden
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
Christopher Jakubowski
Investigator Email
cjakubowsk@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Please Specify
Study Division
Cancer Related - Not Applicable
Categories Mesh Debug
Prostate Cancer --- PROSTATIC NEOPLASMS
Prostate Cancer --- GENITAL NEOPLASMS, MALE
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Prostate Cancer --- PROSTATIC DISEASES
MeSH Terms
PROSTATIC NEOPLASMS
GENITAL NEOPLASMS, MALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
GENITAL DISEASES, MALE
GENITAL DISEASES
UROGENITAL DISEASES
PROSTATIC DISEASES
MALE UROGENITAL DISEASES
PF06821497
ENZALUTAMIDE