An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 228
- 试验地点
- 24
- 主要终点
- Percentage of Participants with Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 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
Dose-Escalation (Part IA): RO6958688 + Atezolizumab
Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
干预措施: Atezolizumab (Drug)
Dose-Escalation (Part IA): RO6958688 + Atezolizumab
Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
干预措施: RO6958688 (Drug)
Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab
Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of:
Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688.
Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab
Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of:
Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688.
Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first.
干预措施: RO6958688 (Drug)
结局指标
主要结局
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Day 1 up to Day 21
Maximum-Tolerated Dose (MTD) of RO6958688
时间窗: Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
Number of Participants with Adverse Events (AEs)
时间窗: Baseline up to 60 months
Recommended Phase II Dose (RP2D) of RO6958688
时间窗: Day 1 up to 60 months
次要结局
- PK: AUC of Atezolizumab(Baseline up to 60 months)
- PK: Cmax of Atezolizumab(Baseline up to 60 months)
- PK: Clearance (CL) of RO6958688(Baseline up to 60 months)
- PK: Vss of Atezolizumab(Baseline up to 60 months)
- Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry(Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days))
- Best Overall Response (BOR)(Baseline up to 60 months)
- PK: Maximum Serum Concentration (Cmax) of RO6958688(Baseline up to 60 months)
- PK: CL of Atezolizumab(Baseline up to 60 months)
- Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])(Baseline up to 60 months)
- Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST(Baseline up to 60 months)
- Duration of Response (DOR) as Assessed Using RECIST(From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months))
- Overall Survival (OS)(From first study treatment to death from any cause (up to 60 months))
- Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688(Baseline up to 60 months)
- PK: Volume of Distribution at Steady State (Vss) of RO6958688(Baseline up to 60 months)
- Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST(Baseline up to 60 months)
- Progression-Free Survival (PFS) according to RECIST V1.1(From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months))