A Phase II Open Label, Dose-finding run-in and Cohort Expansion Study to Evaluate the Safety, Tolerability and Effectiveness of Tinodasertib in Combination With Pembrolizumab or Irinotecan in Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 5
- 主要终点
- Objective response rate based on Response Evaluation Criteria in Solid tumors (RECIST) Version 1.1
研究概览
简要总结
The study is a 2-part study of Tinodasertib alone or in combination with Pembrolizumab/Irinotecan in patients with CRC.
详细描述
The study is conducted in 2 parts. First a dose escalation Run-in to identify the Maximum Tolerable Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Tinodasertib to be administered orally as monotherapy and in combination with intravenous pembrolizumab/irinotecan. Part 2 consists of a cohort expansion at the RP2D of Tinodasertib n combination with intravenous pembrolizumab/Irinotecan in patients with locally advanced or metastatic CRC to evaluate clinical activity and safety of Tinodasertib.
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
- 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
Module 1: Arm A: Multiple dose finding cohorts
Monotherapy with Tinodasertib administered orally QOD
干预措施: Tinodasertib (Drug)
Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan
Combination doses with Tinodasertib administered orally QOD with intravenous pembrolizumab at 200mg Q3W or Irinotecan at 180mg/m2 Q2W
干预措施: Tinodasertib (Drug)
Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan
Combination doses with Tinodasertib administered orally QOD with intravenous pembrolizumab at 200mg Q3W or Irinotecan at 180mg/m2 Q2W
干预措施: Pembrolizumab (Drug)
Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan
Combination doses with Tinodasertib administered orally QOD with intravenous pembrolizumab at 200mg Q3W or Irinotecan at 180mg/m2 Q2W
干预措施: Irinotecan (Drug)
Module 2: Arm B' and C': Dose Expansion
Combination therapy with Tinodasertib administered orally QOD at RP2D (as determined in Module 1) and either pembrolizumab at 200mg IV Q3W (arm B') or irinotecan 180mg/m2 IV Q2W (arm C')
干预措施: Tinodasertib (Drug)
Module 2: Arm B' and C': Dose Expansion
Combination therapy with Tinodasertib administered orally QOD at RP2D (as determined in Module 1) and either pembrolizumab at 200mg IV Q3W (arm B') or irinotecan 180mg/m2 IV Q2W (arm C')
干预措施: Pembrolizumab (Drug)
Module 2: Arm B' and C': Dose Expansion
Combination therapy with Tinodasertib administered orally QOD at RP2D (as determined in Module 1) and either pembrolizumab at 200mg IV Q3W (arm B') or irinotecan 180mg/m2 IV Q2W (arm C')
干预措施: Irinotecan (Drug)
结局指标
主要结局
Objective response rate based on Response Evaluation Criteria in Solid tumors (RECIST) Version 1.1
时间窗: Approximately 2 years from date of participant enrolment
Adverse events and Serious Adverse events
时间窗: Approximately 2 years from date of participant enrolment
Incidence and severity of AEs and SAEs.
Incidence of DLT events and treatment emergent AEs (TEAEs)
时间窗: 1 complete cycle (21 days)
Grading of DLTs according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
次要结局
- PK evaluation(Approximately 6 months from date of participant enrolment)