A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 1,130
- 试验地点
- 60
- 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 combined with Standard(s) of Care (SOC) or with novel agents.
The current subprotocols include the following:
Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens
Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6
Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel
Subprotocol D: RMC-9805 with or without RMC-6236 + 5-fluorouracil-based regimens
Subprotocol E: RMC-9805 with or without RMC-6236 + cetuximab with or without mFOLFOX6
Subprotocol F: RMC-9805 with or without RMC-6236 + gemcitabine + nab-paclitaxel
详细描述
The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents to be evaluated in patients with RAS-mutated solid tumors with a focus on GI cancers.
This is an open-label platform study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC) or with novel agents, and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with RAS mutations will be specified in each subprotocol.
Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with treatment-naïve unresectable or metastatic colorectal cancer or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter study of RMC-6236 in combination with cetuximab with or without mFOLFOX6 in patients with unresectable or metastatic colorectal cancer or patients with previously treated or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol D is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with 5-fluorouracil-based regimens in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol E is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with cetuximab-based therapies with or without mFOLFOX6 in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol F is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with RAS G12D-mutant metastatic pancreatic ductal adenocarcinoma.
Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.
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
- •Pathologically or cytologically documented pancreatic carcinoma or poorly differentiated pancreatic carcinoma with metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A, B, and C)
- •Presence of RAS G12D mutation (Subprotocol D, E, F)
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 within 28 days of first dose
- •Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
干预措施: mFOLFIRINOX regimen (Drug)
Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Bevacizumab with 5-fluorouracil- based regimens
干预措施: mFOLFIRINOX regimen (Drug)
Subprotocol C: metastatic PDAC
RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel
干预措施: RMC-6236 (Drug)
Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Bevacizumab with 5-fluorouracil- based regimens
干预措施: bevacizumab (Drug)
Subprotocol C: metastatic PDAC
RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel
干预措施: nab-paclitaxel (Drug)
Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Bevacizumab with 5-fluorouracil- based regimens
干预措施: RMC-6236 (Drug)
Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Bevacizumab with 5-fluorouracil- based regimens
干预措施: RMC-9805 (Drug)
Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Cetuximab with or without mFOLFOX6
干预措施: RMC-6236 (Drug)
Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Cetuximab with or without mFOLFOX6
干预措施: RMC-6236 (Drug)
Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Cetuximab with or without mFOLFOX6
干预措施: cetuximab (Drug)
Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Cetuximab with or without mFOLFOX6
干预措施: cetuximab (Drug)
Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
干预措施: RMC-6236 (Drug)
Subprotocol C: metastatic PDAC
RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel
干预措施: gemcitabine (Drug)
Subprotocol F: RAS G12D-mutated metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
干预措施: gemcitabine (Drug)
Subprotocol F: RAS G12D-mutated metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
干预措施: RMC-9805 (Drug)
Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
干预措施: bevacizumab (Drug)
Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
干预措施: mFOLFOX6 regimen (Drug)
Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Cetuximab with or without mFOLFOX6
干预措施: mFOLFOX6 regimen (Drug)
Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Bevacizumab with 5-fluorouracil- based regimens
干预措施: mFOLFOX6 regimen (Drug)
Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Cetuximab with or without mFOLFOX6
干预措施: mFOLFOX6 regimen (Drug)
Subprotocol F: RAS G12D-mutated metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
干预措施: nab-paclitaxel (Drug)
Subprotocol F: RAS G12D-mutated metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
干预措施: RMC-6236 (Drug)
Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Cetuximab with or without mFOLFOX6
干预措施: RMC-9805 (Drug)
结局指标
主要结局
Adverse events
时间窗: Up to 3 years
Evaluate the safety and tolerability in the study population characterized by incidence, abnormal laboratory assessments, severity, and seriousness of adverse events in relation to the study treatment.
Dose limiting toxicities
时间窗: 28 days
Number of participants with dose limiting toxicities
次要结局
- Pharmacokinetics of RMC-6236 and RMC-9805(21 weeks)
- ORR(Up to 3 years)
- DOR(Up to 3 years)
- DCR(Up to 3 years)
- PFS(Up to 3 years)
- TTR(Up to 3 years)
- OS(Up to 3 years)