A Phase Ib/II ,Single Arm, Multi-Center, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of JAB-21822 in Advanced or Metastatic Non-small Cell Lung Cancer With a KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 42
- 主要终点
- Dose Escalation phase Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
Evaluate the safety and tolerability, drug levels, and clinical activity of JAB-21822 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors with KRAS p.G12C mutation and a serine/threonine kinase 11 (STK11) co-mutation.
详细描述
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 during Dose Escalation phase and preliminary antitumor activity in patients with NSCLC with concurrent KRAS G12C mutant and STK11 mutant and KEAP wild type either treatment naïve or at least one line prior therapy for advance disease during the expansion phase..
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
- •Pathologically documented, locally-advanced or metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing.
- •STK11 co-mutation and KEAP1 Wild-Type (local confirmation)
- •Treatment naïve or have received at least 1 prior standard therapy for advanced NSCLC
排除标准
- •Has CNS metastases or carcinomatous meningitis, except treated CNS metastases with no evidence of radiographic progression or hemorrhage for at least 28 days
- •Any severe and/or uncontrolled medical conditions
- •Active infection requiring systemic treatment within 7 days
- •Therapeutic radiation therapy within 3 weeks of study day 1
研究组 & 干预措施
Phase 1 ,Dose Exploration ,monotherapy
Dose escalation of JAB21822 will be administered as monotherapy to determine the MTD and RP2D
干预措施: JAB 21822 (Drug)
Phase 2, Dose Expansion, Part1 monotherapy
Part 1 dose expansion is to evaluate the safety and clinical activity of JAB-21822 at RP2D in subjects with previously untreated advanced non-small cell lung cancer (NSCLC)
干预措施: JAB 21822 (Drug)
Phase 2 Dose Expansion, Part 2 monotherapy
Part 2 dose expansion is to evaluate the safety and clinical activity of JAB-21822 at RP2D in subjects who had received at least one previous line of systemic therapy for NSCLC
干预措施: JAB 21822 (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 or abnormal laboratory values assessment during the first 21 days of Cycle 1. It excludes adverse events (AEs) that are deemed clearly related to underlying disease, progression, or intercurrent illness.
Dose Escalation phase: Number of participants with adverse events
时间窗: Up to 3 years
Patients will be assessed for incidence and severity of AEs according to NCI-CTCAE 5.0 criteria
Dose Expansion phase: Objective response rate (ORR)
时间窗: Up to 3 years - from baseline to confirmed Progressive Disease per RECIST.
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: Duration of response (DOR)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Overall Survival (OS)(Up to 3 years)
- Escalation and Dose Expansion phase：Area under the plasma concentration-time curve (AUC)(Up to 3 Years)
- Dose Escalation and Dose Expansion phase: Progression-free survival (PFS)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Time to response (TTR)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Plasma concentration (Cmax)(Up to 3 Years)
- Dose Escalation and Dose Expansion phase: Time to achieve Cmax (Tmax)(Up to 3 Years)
- Dose Escalation and Dose Expansion phase: Disease Control Rate (DCR)(Up to 3 years)
- Dose Escalation phase: Objective response rate (ORR)(Up to 3 years - from baseline to RECIST confirmed Progressive Disease)
- Dose Expansion phase: Number of participants with adverse events(Up to 3 years)