A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 616
- 试验地点
- 160
- 主要终点
- Adverse events
研究概览
简要总结
The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other.
The first four subprotocols include the following:
Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805
详细描述
The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents or as a monotherapy to be evaluated in patients with RAS-mutated solid tumors with a focus on NSCLC.
This is an open-label platform Phase 1b/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC), or as a monotherapy and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with KRAS or RAS mutations will be specified in each subprotocol.
Subprotocol A is an open-label, multicenter, Phase 1b/2 study of RMC-6291, with or without RMC-6236, in combination with pembrolizumab, with or without chemotherapy, in patients with KRAS G12C-mutated advanced solid tumors.
Subprotocol B is an open-label, multicenter, Phase1b/2 study of RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with RAS-mutated non-small cell lung cancer (NSCLC)
Subprotocol C is an open-label, multicenter, Phase1b/2 study of RMC-9805 with or without RMC-6236, in combination with other anticancer agents, in patients with RAS G12D-mutated non-small cell lung cancer (NSCLC)
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
- •All Patients (unless otherwise noted):
- •≥ 18 years of age
- •ECOG PS is 0 to 1
- •Adequate organ function as outlined by the study
- •Received prior standard therapy appropriate for tumor type and stage
- •Must have pathologically documented, locally advanced or metastatic KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A)
- •Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B)
- •Must have pathologically documented, locally advanced or metastatic RAS G12D-mutated NSCLC (Subprotocol C and Subprotocol D)
排除标准
- •All Patients:
- •Primary central nervous system (CNS) tumors
- •Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
- •Major surgery < 28 days of first dose
- •Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids
- •Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: RMC-6291 (Drug)
Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: RMC-6236 (Drug)
Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Pembrolizumab (Drug)
Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Cisplatin (Drug)
Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Carboplatin (Drug)
Subprotocol B: RAS-mutated NSCLC
RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: RMC-6236 (Drug)
Subprotocol B: RAS-mutated NSCLC
RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Cisplatin (Drug)
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
干预措施: Carboplatin (Drug)
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
干预措施: Pemetrexed (Drug)
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
干预措施: RMC-6236 (Drug)
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
干预措施: RMC-9805 (Drug)
Subprotocol D: RAS G12D-mutated NSCLC
RMC-9805 (QD)
干预措施: RMC-9805 (Drug)
Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Pemetrexed (Drug)
Subprotocol B: RAS-mutated NSCLC
RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Pembrolizumab (Drug)
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
干预措施: Pembrolizumab (Drug)
Subprotocol B: RAS-mutated NSCLC
RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Carboplatin (Drug)
Subprotocol B: RAS-mutated NSCLC
RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
干预措施: Pemetrexed (Drug)
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
干预措施: Cisplatin (Drug)
结局指标
主要结局
Adverse events
时间窗: Up to 5 years
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs and vital signs
Dose limiting toxicities
时间窗: 21 days
Number of participants with dose limiting toxicities
次要结局
- Tmax(Up to 21 weeks)
- Drug concentrations over time(Up to 21 weeks)
- AUC(Up to 21 weeks)
- Cmax(Up to 21 weeks)
- ORR(Up to 5 years)
- DOR(Up to 5 years)
- Drug concentrations over time(Up to 21 weeks)
- Cmax(Up to 21 weeks)
- Tmax(Up to 21 weeks)
- AUC(Up to 21 weeks)
- ORR(Up to 5 years)
- DOR(Up to 5 years)