Study of RAS(ON) Inhibitors in Patients with Gastrointestinal Solid Tumors
Purpose
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 first three 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
Conditions
- Colorectal Cancer
- CRC
- Pancreatic Ductal Adenocarcinoma
- PDAC
- Gastrointestinal Cancer
- Metastatic Pancreatic Ductal Adenocarcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
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)
Exclusion Criteria
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.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC |
RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens |
|
|
Experimental Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC |
RMC-6236 (QD) and Cetuximab with or without mFOLFOX6 |
|
|
Experimental Subprotocol C: metastatic PDAC |
RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Revolution Medicines, Inc.
Detailed Description
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. Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.