Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 574
- 试验地点
- 9
- 主要终点
- Number of patients with adverse events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.
详细描述
This is an open-label, multicenter, Phase 1/1b study of RMC-5127 in adults with advanced KRAS G12V-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: RMC-5127 monotherapy arm, RMC-5127 plus daraxonrasib combination arm, and RMC-5127 plus cetuximab combination arm. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Both parts of the monotherapy arm may include Food Effect Cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •At least 18 years old and has provided informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Pathologically documented, locally advanced or metastatic KRAS G12V-mutated solid tumor malignancy.
- •Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage.
- •Measurable per RECIST v1.1
- •Adequate organ function (bone marrow, liver, kidney, coagulation).
- •Able to take oral medications.
排除标准
- •Primary central nervous system (CNS) tumors
- •Prior therapy with KRAS G12V inhibitor or direct RAS-targeted therapy (eg. degraders and/or inhibitors).
- •Any conditions that may affect the ability to take or absorb study drug.
- •Major surgery within 28 days prior to receiving study drug(s).
- •Patient is unable or unwilling to comply with protocol-required study visits or procedures.
研究组 & 干预措施
Arm A: RMC-5127 Monotherapy
Dose Escalation and Dose Expansion
干预措施: RMC-5127 (Drug)
Arm B: RMC-5127 + Daraxonrasib Combination
Dose Escalation and Dose Expansion
干预措施: daraxonrasib (Drug)
Arm C: RMC-5127 + Cetuximab Combination
Dose Escalation and Dose Expansion
干预措施: RMC-5127 (Drug)
Arm C: RMC-5127 + Cetuximab Combination
Dose Escalation and Dose Expansion
干预措施: cetuximab (Drug)
Arm B: RMC-5127 + Daraxonrasib Combination
Dose Escalation and Dose Expansion
干预措施: RMC-5127 (Drug)
结局指标
主要结局
Number of patients with adverse events (AEs)
时间窗: Up to approximately 3 years
Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5
Changes in vital signs
时间窗: Up to approximately 3 years
Number of patients with changes from baseline in vital signs
Changes in electrocardiogram (ECG) test values
时间窗: Up to approximately 3 years
Number of patients with changes from baseline in ECG test values
Changes in clinical laboratory test values
时间窗: Up to approximately 3 years
Number of patients with changes from baseline in clinical laboratory test values
Dose Limiting Toxicities
时间窗: Up to 28 days
Number of patients with dose limiting toxicities
次要结局
- Cmax concentrations of RMC-5127 and daraxonrasib(Up to Cycle 5 Day 1 (each cycle is up to 28 days))
- Tmax concentration of RMC-5127 and daraxonrasib(Up to Cycle 5 Day 1 (each cycle is up to 28 days))
- AUC concentrations of RMC-5127 and daraxonrasib(Up to Cycle 5 Day 1 (each cycle is up to 28 days))
- Ratio of accumulation of RMC-5127(Up to Cycle 5 Day 1 (each cycle is up to 28 days))
- Half-Life of RMC-5127 and daraxonrasib(Up to Cycle 5 Day 1 (each cycle is up to 28 days))
- Objective Response Rate (ORR)(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)