A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined With Enzalutamide or Abiraterone/Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 175
- 试验地点
- 41
- 主要终点
- Efficacy: Best Objective Response Rate Percent by Treatment Group
研究概览
简要总结
This was an open-label Phase 1b/2 study involving oral administration of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone in male patients with metastatic Castration-Resistant Prostate Cancer. The study was designed to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) based on the safety, tolerability, pharmacokinetic, and efficacy profiles of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone.
Following the determination of the MTD and RP2D, the study proceeded to Phase 2. Patients in Phase 2 received CPI-1205 at the RP2D in combination with either enzalutamide or abiraterone/prednisone versus either enzalutamide or abiraterone/prednisone as a control arm.
详细描述
Study CPI-1205-201 was a Phase 1b/2, multi-center, open-label study of CPI-1205 alone and with cobicistat in subjects with mCRPC in combination with either enzalutamide or abiraterone/prednisone. The study initially had two phases: a Phase 1 dose-finding, dose-escalation study intended to establish the Recommended Phase 2 Dose (RP2D) of CPI-1205 for the Phase 2 portion.
The study underwent three amendments.
PHASE 1b In the Phase 1b dose-escalation phase and prior to Amendment 2, subjects were enrolled into Phase 1b dose level CPI-1205 PO three times daily (TID) + enzalutamide or abiraterone/prednisone.
In Amendment 2, new subjects were enrolled into cohorts including:
Dose-escalating CPI-1205 PO twice daily (BID) + fixed-dose cobicistat PO BID + enzalutamide Dose-escalating CPI-1205 PO BID + fixed-dose cobicistat PO BID + abiraterone/prednisone In Amendment 3, Phase 1b expansion cohort(s) were added in the heavily pretreated population (HPEC). An HPEC began enrollment if 0 out of 3 or 1 out of 6 subjects treated with a specific regimen (i.e., CPI-1205 with or without cobicistat, in combination with enzalutamide or abiraterone) at a given dose level during Phase 1b dose escalation experienced a dose-limiting toxicity (DLT).
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
- None
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles)
干预措施: CPI-1205 (Drug)
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles)
干预措施: Cobicistat (Drug)
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles)
干预措施: Enzalutamide (Drug)
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: CPI-1205 (Drug)
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: Cobicistat (Drug)
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: Abiraterone (Drug)
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred
CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: Prednisone (Drug)
Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza
CPI-1205 800 mg TID in combination with Enzalutamide 160 mg PO QD (28-day cycle)
干预措施: CPI-1205 (Drug)
Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza
CPI-1205 800 mg TID in combination with Enzalutamide 160 mg PO QD (28-day cycle)
干预措施: Enzalutamide (Drug)
Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred
CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: CPI-1205 (Drug)
Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred
CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: Abiraterone (Drug)
Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred
CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
干预措施: Prednisone (Drug)
Phase 1b HPEC: CPI-1205 800 mg TID + Enza
CPI-1205 800 mg TID highly pretreated expansion cohort (HEPC) in combination with Enzalutamide 160 mg PO QD (28-day cycles)
干预措施: CPI-1205 (Drug)
Phase 1b HPEC: CPI-1205 800 mg TID + Enza
CPI-1205 800 mg TID highly pretreated expansion cohort (HEPC) in combination with Enzalutamide 160 mg PO QD (28-day cycles)
干预措施: Enzalutamide (Drug)
Phase 2 Randomized Controlled Group: Enza
Drug: Enzalutamide 160mg PO QD (28-day cycles)
干预措施: Enzalutamide (Drug)
Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza
CPI-1205 (at Recommended Phase 2 Dose [RP2D]) in combination with Drug: Enzalutamide 160 mg PO QD
干预措施: CPI-1205 (Drug)
Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza
CPI-1205 (at Recommended Phase 2 Dose [RP2D]) in combination with Drug: Enzalutamide 160 mg PO QD
干预措施: Enzalutamide (Drug)
Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred
CPI-1205 at 800 mg TID (Recommended Phase 2 Dose [RP2D]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles)
干预措施: CPI-1205 (Drug)
Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred
CPI-1205 at 800 mg TID (Recommended Phase 2 Dose [RP2D]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles)
干预措施: Abiraterone (Drug)
Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred
CPI-1205 at 800 mg TID (Recommended Phase 2 Dose [RP2D]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles)
干预措施: Prednisone (Drug)
结局指标
主要结局
Efficacy: Best Objective Response Rate Percent by Treatment Group
时间窗: Up to 2 years [or until disease progression or unacceptable toxicity]
Best overall response rate (%) defined as complete response (CR) + partial response (PR) divided by the total number of subjects as assessed by Investigator. The response assessment was performed per Prostate Cancer Working Group 3 (PCWG3) based on modifications of the RECIST 1.1 criteria. Per RECIST 1.1, a CR was assessed when all target lesions disappeared (any pathological lymph node must have reduction in short axis to \<10 mm) in the post-baseline scan. A PR was assessed when there was at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Efficacy: Percentage (%) of Subjects With PSA30
时间窗: 2 years [or until progressive disease or unacceptable toxicity]
The number of subjects who had a confirmed reduction of 30% of prostate-specific antigen (PSA30) from baseline
Efficacy: Percentage (%) of Subjects With PSA50
时间窗: 2 years [or until progressive disease or unacceptable toxicity]
The number of subjects who had a confirmed reduction of 50% of prostate-specific antigen (PSA50) from baseline
Efficacy: Composite Response Rate (%) for Phase 2 Randomized and Phase 2 Single-arm Treatment Groups
时间窗: Up to 2 years [or until progressive disease or unacceptable toxicity]
Subjects who had a circulating tumor cell of 30% (CTC 30%) or an objective response rate divided by the number of evaluable subjects
次要结局
- Efficacy: Best Responses by Treatment Group(Up to 2 years [or until disease progression or unacceptable toxicity])
- Safety: Number of Participants With Treatment-emergent AEs Leading to Treatment Discontinuation(Up to 2 years [or until clinical progression, radiographic disease progression, or until unacceptable toxicity])