A Phase Ib/II Trial of JAB-21822 in Combination With Cetuximab in Patients With Advanced Colorectal Cancer, Small Intestine Cancer and Appendiceal Cancer With KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 17
- 主要终点
- Dose Escalation phase: Number of participants with dose-limiting toxicities (DLTs)
研究概览
简要总结
This study is to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of JAB-21822 in combination with cetuximab in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.
详细描述
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 in combination with cetuximab to determine the MTD and RP2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 is administered in combination with cetuximab during Dose Expansion phase in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Participants must be able to provide an archived tumor sample
- •Histologically or cytologically confirmed advanced colorectal cancer, advanced small intestinal cancer and advanced appendiceal cancer with KRAS p.G12C mutation
- •Must have received at least 1 prior standard therapy
- •Must have at least 1 measurable lesion per RECIST v1.1
- •Must have adequate organ function
- •Must be able to swallow and retain orally administered medication
排除标准
- •Has brain metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days
- •Active infection requiring systemic treatment within 14 days
- •Active HIV, HBV or HCV
- •Any severe and/or uncontrolled medical conditions
- •LVEF<50% assessed by ECHO
- •QT interval >470 msec
研究组 & 干预措施
Phase 1b Dose Escalation
Dose escalation of JAB-21822 to determine maximum tolerated dose of JAB-21822 in combination with cetuximab.
干预措施: JAB-21822 (Drug)
Phase 1b Dose Escalation
Dose escalation of JAB-21822 to determine maximum tolerated dose of JAB-21822 in combination with cetuximab.
干预措施: Cetuximab (Drug)
Phase 2 Dose Expansion, Cohort 1
Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
干预措施: JAB-21822 (Drug)
Phase 2 Dose Expansion, Cohort 1
Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
干预措施: Cetuximab (Drug)
Phase 2 Dose Expansion, Cohort 2
Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced small intestinal cancer and advanced appendiceal cancer.
干预措施: JAB-21822 (Drug)
Phase 2 Dose Expansion, Cohort 2
Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced small intestinal cancer and advanced appendiceal cancer.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Dose Escalation phase: Number of participants with dose-limiting toxicities (DLTs)
时间窗: At the end of Cycle 1 (each cycle is 21 days)
A DLT is defined as the clinically significant treatment related adverse event (TRAE) or abnormal laboratory values assessment during the first 21 days of (Cycle 1) and excludes events that are deemed clearly related to underlying disease, progression, or intercurrent illness.
Dose Expansion phase: Overall response rate (ORR)
时间窗: Up to 4 years - from baseline to RECIST confirmed Progressive Disease
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1.
次要结局
- Dose Escalation and Dose Expansion phase: Number of participants with adverse events(Up to 4 years)
- Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC)(Up to 4 years)
- Dose Escalation phase: Overall response rate (ORR)(Up to 4 years)
- Dose Expansion phase: Progression-free survival (PFS)(Up to 4 years)
- Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax)(Up to 4 years)
- Dose Expansion phase: Disease Control Rate ( DCR )(Up to 4 years)
- Dose Expansion phase: Duration of response ( DOR )(Up to 4 years)