A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF MEVROMETOSTAT (PF-06821497) WITH ENZALUTAMIDE IN METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MEVPRO-3)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 1,000
- 试验地点
- 388
- 主要终点
- Radiographic Progression Free Survival (rPFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study. Participants will receive mevrometostat or matching placebo in a blinded fashion. Participants, investigators and site staff, and sponsor staff will be aware that participants in both study arms are receiving enzalutamide. Enzalutamide will be provided in an open-label manner to participants in each treatment arm.
Participants and their caregivers will be blinded to their assigned study intervention.
Investigators and other site staff will be blinded to participants' assigned study intervention Sponsor staff will be blinded to participants' assigned study intervention, except for sponsor staff involved in the assignment or distribution of study intervention.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •Use of 5-alpha reductase inhibitors is prohibited within 28 days of randomization.
- •Prior surgery from which the participant has not fully recovered at least 28 days prior to randomization
- •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.
- •Known allergic or hypersensitivity reactions to mevrometostat or its excipients or to enzalutamide or its excipients.
研究组 & 干预措施
Arm A
Participants will receive mevrometostat/PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Mevrometostat (Drug)
Arm B
Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Placebo (Drug)
Arm A
Participants will receive mevrometostat/PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Enzalutamide (Drug)
Arm B
Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Radiographic Progression Free Survival (rPFS)
时间窗: Randomization up to approximately 4 years
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.
次要结局
- Prostate Specific Antigen Response, Undetectable PSA after Randomization(Randomization up to approximately 4 years)
- Overall survival (OS)(Randomization up to approximately 9 years)
- Objective response in measurable soft tissue disease(Randomization up to approximately 4 years)
- Duration of Response (DoR) in measurable soft tissue disease(Randomization up to approximately 4 years)
- Prostate Specific Antigen Response(Randomization up to approximately 4 years)
- Time to prostate specific antigen (PSA) progression(Randomization up to approximately 4 years)
- Time to initiation of antineoplastic therapy(Randomization up to approximately 4 years)
- Time to first symptomatic skeletal event(Randomization up to approximately 4 years)
- Time from randomization to CRPC(Randomization up to approximately 4 years)
- Incidence of Adverse Events(Randomization up to approximately 5 years)
- To evaluate the PK of mevrometostat when dosed in combination with enzalutamide(Cycle 3 Day 1 to last PK draw at Cycle 5 Day 1 (cycle length is 28 days))
- Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)(Randomization up to approximately 5 years)
- Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)(Randomization up to approximately 5 years)
- Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P(Randomization up to approximately 5 years)
- Patient-reported outcomes in cancer specific symptoms - time to definitive deterioration(Randomization up to approximately 5 years)
- Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms per BFI(Randomization up to approximately 5 years)
- Change from baseline in participant-reported general health status per EQ-5D-5L(Randomization up to approximately 5 years)
- To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden(Baseline up to approximately 4 years)