A Phase Ib Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab, To Patients With Advanced Platinum-sensitive Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 20
- 主要终点
- Investigator-assessed confirmed objective response rate (ORR)
研究概览
简要总结
The study will include a safety run-in phase (Stage 1) and a randomization phase (Stage 2).
The purpose of Stage 1 is to evaluate the safety of cobimetinib when administered in combination with niraparib (Cohort 1) and cobimetinib with niraparib plus atezolizumab (Cohort 2).
Stage 1 will enable patient enrollment in the randomized phase of the study (Stage 2) with both regimens at the recommended dose levels from Stage 1.
Stage 2 is a randomized, dose-expansion phase, evaluating clinical outcomes in patients with advanced platinum-sensitive ovarian cancer.
All patients will continue to receive study treatment until disease progression (according to "Response Evaluation Criteria in Solid Tumors" (RECIST), Version 1.1, unacceptable toxicity, death, or patient or investigator decision to withdraw, whichever occurs first.
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
- Female
- 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
Arm A: Cobimetinib - Niraparib
Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1, Cohort 1.
干预措施: Cobimetinib (Drug)
Arm A: Cobimetinib - Niraparib
Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1, Cohort 1.
干预措施: Niraparib (Drug)
Arm B: Cobimetinib - Niraparib - Atezolizumab
Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Arm B: Cobimetinib - Niraparib - Atezolizumab
Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
干预措施: Niraparib (Drug)
Arm B: Cobimetinib - Niraparib - Atezolizumab
Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 1 - Cobimetinib - Niraparib
Stage 1 - Patients in Cohort 1 will be treated with cobimetinib plus niraparib.
Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle.
Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 2 - Cobimetinib - Niraparib - Atezolizumab
Stage 1 - Patients in Cohort 2 will be treated with cobimetinib plus niraparib and atezolizumab.
Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle.
Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle.
Atezolizumab: Patients will also receive atezolizumab administered as an IV infusion at a fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
干预措施: Cobimetinib (Drug)
结局指标
主要结局
Investigator-assessed confirmed objective response rate (ORR)
时间窗: From baseline up to 48 months
The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of investigator-assessed confirmed ORR, as determined using RECIST v1.1 in the Intention To Treat (ITT) population and in molecularly defined subgroups by loss of heterozygosity (LOH) status.
Number of patients reporting Adverse Events (AEs)
时间窗: From baseline up to 48 months
The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of number of patients reporting serious and non-serious AEs with severity graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI - CTCAE v5.0)
Change from baseline in targeted clinical laboratory test results
时间窗: From baseline up to 48 months
The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumabwill be evaluated in terms of number of patients reporting change from baseline in targeted clinical laboratory test results.
次要结局
- Serum concentration of atezolizumab(Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months)
- Number of patients with Anti-Drug Antibodies (ADA)(Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months)
- Progression-free survival (PFS)(From Baseline up to 48 months)
- Duration of response (DOR)(From baseline up to 48 months)
- Overall survival (OS)(From baseline up to 48 months)
- Plasma concentration of cobimetinib and niraparib(Arm A: Day 15 of Cycle 1 and 2 - Arm B: Day 15 of Cycle 1)