Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
1 other identifier
interventional
1,130
1 country
32
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 colorectal-cancer
Started May 2024
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2024
CompletedStudy Start
First participant enrolled
May 24, 2024
CompletedFirst Posted
Study publicly available on registry
June 6, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 15, 2027
April 1, 2026
December 1, 2025
3 years
May 20, 2024
March 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Adverse events
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.
Up to 3 years
Dose limiting toxicities
Number of participants with dose limiting toxicities
28 days
Secondary Outcomes (7)
Pharmacokinetics of RMC-6236 and RMC-9805
21 weeks
ORR
Up to 3 years
DOR
Up to 3 years
DCR
Up to 3 years
TTR
Up to 3 years
- +2 more secondary outcomes
Study Arms (6)
Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
EXPERIMENTALRMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
EXPERIMENTALRMC-6236 (QD) and Cetuximab with or without mFOLFOX6
Subprotocol C: metastatic PDAC
EXPERIMENTALRMC-6236 (QD) and Gemcitabine with Nab-paclitaxel
Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
EXPERIMENTALRMC-9805 (QD or BID) with or without RMC-6236 (QD), and Bevacizumab with 5-fluorouracil- based regimens
Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
EXPERIMENTALRMC-9805 (QD or BID) with or without RMC-6236 (QD), and Cetuximab with or without mFOLFOX6
Subprotocol F: RAS G12D-mutated metastatic PDAC
EXPERIMENTALRMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
Interventions
Oral tablet
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
Oral Tablet
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (32)
Ironwood Cancer and Research Centers
Chandler, Arizona, 85224, United States
Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
HonorHealth Research Institute
Scottsdale, Arizona, 85258, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Cedars-Sinai Cancer at Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
UCLA Hematology/Oncology- Santa Monica
Los Angeles, California, 90404, United States
University of Colorado Hospital-Anschutz Cancer Pavilion
Aurora, Colorado, 88045, United States
Yale-New Haven Hospital-Yale Cancer Center
New Haven, Connecticut, 06520, United States
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
The University of Kansas Clinical Research Center
Westwood, Kansas, 66205, United States
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Atlantic Health System
Morristown, New Jersey, 07960, United States
Northwell Health / RJ Zuckerberg Cancer Center
Lake Success, New York, 11042, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center Main Campus
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
SCRI Oncology Partners
Nashville, Tennessee, 37203, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
NEXT Oncology Dallas
Irving, Texas, 75039, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22314, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
Related Publications (1)
Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J Med Chem. 2025 Mar 27;68(6):6064-6083. doi: 10.1021/acs.jmedchem.4c02314. Epub 2025 Mar 8.
PMID: 40056080DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Study Director
Revolution Medicines
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 20, 2024
First Posted
June 6, 2024
Study Start
May 24, 2024
Primary Completion (Estimated)
May 15, 2027
Study Completion (Estimated)
July 15, 2027
Last Updated
April 1, 2026
Record last verified: 2025-12