A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 4
- 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 and tolerability of JAB-21822 monotherapy and combination therapy in adult participants with advanced solid tumors harboring KRAS G12C mutation.
详细描述
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 monotherapy to determine the MTD and PR2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 administered alone and combination with cetuximab during Dose Expansion phase in adult participants with advanced solid tumors harboring KRAS 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 solid tumors with KRAS 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 or spinal metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days
- •Active infection requiring systemic treatment within 7 days
- •Active HBV or HCV
- •Any severe and/or uncontrolled medical conditions
- •LVEF ≤50% assessed by ECHO or QTcF
- •QT interval >470 msec
- •Experiencing unresolved CTCAE 5.0 Grade >1 toxicities
研究组 & 干预措施
Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion
JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity.
干预措施: Cetuximab (EGFR inhibitor) (Drug)
Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion
JAB-21822 will be administered alone at RP2D in selected cancer type patients to evaluate the preliminary antitumor activity.
干预措施: JAB-21822 (KRAS G12C inhibitor) (Drug)
Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion
JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity.
干预措施: JAB-21822 (KRAS G12C inhibitor) (Drug)
Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation
Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D
干预措施: JAB-21822 (KRAS G12C inhibitor) (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)
Dose Escalation and Dose Expansion phase: Number of participants with adverse events
时间窗: Up to 4 years
Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria
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
Dose Expansion phase: Duration of response ( DOR )
时间窗: Up to 4 years
DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first.
次要结局
- Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax)(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 - from baseline to RECIST confirmed Progressive Disease)
- Dose Escalation phase: Duration of response ( DOR )(Up to 4 years)
- Dose Escalation and Dose Expansion phase: Disease Control Rate ( DCR )(Up to 4 years)
- Dose Escalation and Dose Expansion phase: Progression-free survival (PFS)(Up to 4 years)