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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 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

Conditions

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) - Presence of RAS G12D mutation (Subprotocol D, E, F)

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

ArmDescriptionAssigned Intervention
Experimental
Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC 		RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
  • Drug: RMC-6236
    Oral tablet
  • Drug: mFOLFOX6 regimen
    IV infusion
  • Drug: bevacizumab
    IV infusion
  • Drug: mFOLFIRINOX regimen
    IV infusion
Experimental
Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC 		RMC-6236 (QD) and Cetuximab with or without mFOLFOX6
  • Drug: RMC-6236
    Oral tablet
  • Drug: mFOLFOX6 regimen
    IV infusion
  • Drug: cetuximab
    IV infusion
Experimental
Subprotocol C: metastatic PDAC 		RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel
  • Drug: RMC-6236
    Oral tablet
  • Drug: gemcitabine
    IV infusion
  • Drug: nab-paclitaxel
    IV infusion
Experimental
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
  • Drug: RMC-6236
    Oral tablet
  • Drug: mFOLFOX6 regimen
    IV infusion
  • Drug: bevacizumab
    IV infusion
  • Drug: mFOLFIRINOX regimen
    IV infusion
  • Drug: RMC-9805
    Oral Tablet
Experimental
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
  • Drug: RMC-6236
    Oral tablet
  • Drug: mFOLFOX6 regimen
    IV infusion
  • Drug: cetuximab
    IV infusion
  • Drug: RMC-9805
    Oral Tablet
Experimental
Subprotocol F: RAS G12D-mutated metastatic PDAC 		RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
  • Drug: RMC-6236
    Oral tablet
  • Drug: gemcitabine
    IV infusion
  • Drug: nab-paclitaxel
    IV infusion
  • Drug: RMC-9805
    Oral Tablet

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Emma Crooks
(617) 724-9737
ecrooks1@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Revolution Medicines, Inc.

Study Contact

Revolution Medicines
1-844-2-REVMED
medinfo@revmed.com

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. 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.