Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
NCT ID: NCT06445062
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
1130 participants
INTERVENTIONAL
2024-05-24
2027-07-15
Brief Summary
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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
Detailed Description
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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.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens
RMC-6236
Oral tablet
mFOLFOX6 regimen
IV infusion
bevacizumab
IV infusion
mFOLFIRINOX regimen
IV infusion
Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and Cetuximab with or without mFOLFOX6
RMC-6236
Oral tablet
mFOLFOX6 regimen
IV infusion
cetuximab
IV infusion
Subprotocol C: metastatic PDAC
RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel
RMC-6236
Oral tablet
gemcitabine
IV infusion
nab-paclitaxel
IV infusion
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
RMC-6236
Oral tablet
mFOLFOX6 regimen
IV infusion
bevacizumab
IV infusion
mFOLFIRINOX regimen
IV infusion
RMC-9805
Oral Tablet
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
RMC-6236
Oral tablet
mFOLFOX6 regimen
IV infusion
cetuximab
IV infusion
RMC-9805
Oral Tablet
Subprotocol F: RAS G12D-mutated metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and Gemcitabine with Nab-paclitaxel
RMC-6236
Oral tablet
gemcitabine
IV infusion
nab-paclitaxel
IV infusion
RMC-9805
Oral Tablet
Interventions
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RMC-6236
Oral tablet
mFOLFOX6 regimen
IV infusion
bevacizumab
IV infusion
mFOLFIRINOX regimen
IV infusion
cetuximab
IV infusion
gemcitabine
IV infusion
nab-paclitaxel
IV infusion
RMC-9805
Oral Tablet
Eligibility Criteria
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Inclusion Criteria
* ≥ 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
* 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
18 Years
ALL
No
Sponsors
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Revolution Medicines, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Study Director
Role: STUDY_DIRECTOR
Revolution Medicines
Locations
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Ironwood Cancer and Research Centers
Chandler, Arizona, United States
Mayo Clinic Hospital
Phoenix, Arizona, United States
HonorHealth Research Institute
Scottsdale, Arizona, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Cedars-Sinai Cancer at Cedars-Sinai Medical Center
Los Angeles, California, United States
UCLA Hematology/Oncology- Santa Monica
Los Angeles, California, United States
University of Colorado Hospital-Anschutz Cancer Pavilion
Aurora, Colorado, United States
Yale-New Haven Hospital-Yale Cancer Center
New Haven, Connecticut, United States
Mayo Clinic Cancer Center
Jacksonville, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
The University of Kansas Clinical Research Center
Westwood, Kansas, United States
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Nebraska Cancer Specialists
Omaha, Nebraska, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Atlantic Health System
Morristown, New Jersey, United States
Northwell Health / RJ Zuckerberg Cancer Center
Lake Success, New York, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center Main Campus
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology Dallas
Irving, Texas, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States
Countries
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Central Contacts
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Facility Contacts
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Research Department
Role: primary
Role: primary
Andrea House
Role: primary
Andrea Galfo
Role: primary
Naomi Geier
Role: primary
Jenna Davis
Role: primary
Emily Harper
Role: primary
Stefanie Diaz
Role: primary
Kwasi Boateng
Role: backup
Role: primary
Nilufar Aliyeva
Role: primary
Role: primary
Colleen Apostol
Role: primary
Joann Santmyer
Role: backup
Emma Crooks
Role: primary
Gayane Pogosyan
Role: backup
Asami Castellano
Role: primary
Role: primary
Ashley Servais
Role: primary
Evan Roberts
Role: backup
Mahdi Hassan
Role: primary
Monica Davis
Role: backup
Salome Geene
Role: primary
Tracey Hilden
Role: backup
Deeksha Kaura
Role: primary
Role: primary
Brooke Currier
Role: primary
Role: primary
Christina Caldwell
Role: primary
Jimar Hill
Role: primary
Henry Atencio
Role: primary
Glenn Wilson
Role: backup
Role: primary
Idara Ukpong
Role: primary
Susan Sharry
Role: primary
Karina Castillo
Role: primary
Matt Sherman
Role: primary
References
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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.
Other Identifiers
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RMC-GI-102
Identifier Type: -
Identifier Source: org_study_id