Phase 1b/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Patients With Advanced KRAS G12C-Mutated Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 534
- 试验地点
- 57
- 主要终点
- Number of patients with adverse events (AEs) in Phase 1b
研究概览
简要总结
This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.
详细描述
This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.
The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.
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
盲法说明
None (Open Label)
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
- •18 years of age
- •Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy
- •Phase 1b Dose Escalation: solid tumors, previously treated
- •Phase 1b Dose Expansion and Phase 2:
- •i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.
- •ECOG performance status 0 or 1
- •Adequate organ function
排除标准
- •Primary central nervous system (CNS) tumors
- •Active brain metastases
- •Known impairment of GI function that would alter the absorption
- •Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment
研究组 & 干预措施
Elironrasib Monotherapy
Phase 2 only
干预措施: Elironrasib (Drug)
Daraxonrasib Monotherapy
Phase 2 only
干预措施: Daraxonrasib (Drug)
Daraxonrasib + Elironrasib Combination
Phase 1b and 2
干预措施: Elironrasib (Drug)
Daraxonrasib + Elironrasib Combination
Phase 1b and 2
干预措施: Daraxonrasib (Drug)
结局指标
主要结局
Number of patients with adverse events (AEs) in Phase 1b
时间窗: Up to approximately 3 years
Incidence and severity of treatment-emergent AEs and serious AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5
Changes in vital signs in Phase 1b
时间窗: Up to approximately 3 years
Number of patients with clinically significant changes in vital signs
Changes in clinical laboratory test values in Phase 1b
时间窗: Up to approximately 3 years
Number of patients with clinically significant changes in clinical laboratory test values
Dose Limiting Toxicities in Phase 1b
时间窗: 21 days
Number of participants with dose limiting toxicities
Changes in ECGs in Phase 1b
时间窗: Up to approximately 3 years
Number of patients with clinically significant changes in ECGs
Overall Response Rate (ORR) in Phase 2
时间窗: Up to approximately 3 years
Overall response rate per RECIST v1.1 as assessed by blinded independent central review (BICR)
次要结局
- Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib(up to 21 weeks)
- Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib(up to 21 weeks)
- Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib(up to 21 weeks)
- Elimination Half-Life of Elironrasib and Daraxonrasib(up to 21 weeks)
- Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing(up to 21 weeks)
- Overall Response Rate (ORR) in Phase 1b(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)
- Disease Control Rate in Phase 1b(Up to approximately 3 years)
- Time to Response (TTR) in Phase 1b(Up to approximately 3 years)
- Progression-Free Survival (PFS)(Up to approximately 3 years)
- Number of patients with AEs in Phase 2(Up to approximately 3 years)
- Changes in vital signs in Phase 2(Up to approximately 3 years)
- Changes in clinical laboratory values in Phase 2(Up to approximately 3 years)
- Overall Survival (OS) in Phase 2(Up to approximately 3 years)