Colorectal CancerPhase 1/2NCT06445062
Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
A Phase 1/2 study testing RMC-6236, mFOLFOX6 regimen and bevacizumab in people with Colorectal Cancer and CRC, run by Revolution Medicines, Inc. at 32 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, CRC, Pancreatic Ductal Adenocarcinoma
- What is being tested?
- RMC-6236, mFOLFOX6 regimen and bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,130 participants
- Where
- 32 sitesUnited States
- Study dates
- 24 May 2024to 30 Mar 2030
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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, C and G)
- Presence of RAS G12D mutation (Subprotocol D, E, F, G)
Who cannot join
- 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.
Trial locations and contacts
32 sites in 1 country. Contact the study team or a site near you to ask about taking part.
32 sites in 1 country
United States32 sites, 32 recruiting
- Recruiting
University of Colorado Hospital-Anschutz Cancer Pavilion
Aurora, Colorado, 88045
Emily Harper, (303) 724-9407, Emily.harper@cuanschutz.edu
- Recruiting
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, 21287
Colleen Apostol, 410-614-3644, giclinicaltrials@jhmi.edu
Joann Santmyer, 410-614-3644, giclinicaltrials@jhmi.edu
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Aparna Parikh, (617) 724-4000, Aparna.Parikh@MGH.HARVARD.EDU
Bennett Caughey, (617) 724-4000, bcaughey1@mgb.org
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Charlotte Healy, 617-632-5728, charlotte_healy@dfci.harvard.edu
- Recruiting
Ironwood Cancer and Research Centers
Chandler, Arizona, 85224
Research Department, 480-398-7671, research@ironwoodcrc.com
- Recruiting
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
513-584-7698, cancer@uchealth.com
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Brooke Currier, 919-668-1861, gi-oncology-cru@dm.duke.edu
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22314
Karina Castillo, 571.350.8758, Karina.CastilloGrady@usoncology.com
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
Henry Atencio, 713-798-3743, phase1dldccc@bcm.edu
Glenn Wilson, 713-798-3468, phase1dldccc@bcm.edu
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
GIClinicalTrials@mdanderson.org
- Recruiting
NEXT Oncology Dallas
Irving, Texas, 75039
Idara Ukpong, 972.893.8800, iukpong@nextoncology.com
- Recruiting
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224
855-776-0015, mayocliniccancerstudies@mayo.edu
- Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Andrea Galfo, 858-822-4500, agalfo@health.com
- Recruiting
Northwell Health / RJ Zuckerberg Cancer Center
Lake Success, New York, 11042
Deeksha Kaura, 516-734-8906, GITrialReferral@northwell.edu
- Recruiting
Cedars-Sinai Cancer at Cedars-Sinai Medical Center
Los Angeles, California, 90048
Naomi Geier, 310-423-4693, naomi.geier@cshs.org
- Recruiting
UCLA Hematology/Oncology- Santa Monica
Los Angeles, California, 90404
Jenna Davis, (310) 633-8400 ext. 16128, jldavis@mednet.ucla.edu
- Recruiting
Atlantic Health System
Morristown, New Jersey, 07960
Salome Geene, 973-971-6373, salome.geene@atlantichelath.org
Tracey Hilden, 973-971-7889, tracey.hilden@atlantichealth.org
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Yale-New Haven Hospital-Yale Cancer Center
New Haven, Connecticut, 06520
Stefanie Diaz, 475-227-1088, Stefanie.Diaz@yale.edu
Kwasi Boateng, 203-314-7948, Kwasi.Boateng@yale.edu
- Recruiting
Columbia University Medical Center
New York, New York, 10032
212-342-5162, cancerclinicaltrials@cumc.columbia.edu
- Recruiting
Memorial Sloan Kettering Cancer Center Main Campus
New York, New York, 10065
- Recruiting
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Christina Caldwell, 405-271-8001 ext. 48171, Christina-Caldwell@ouhsc.edu
- Recruiting
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Ashley Servais, 4029552691, aservais@nebraskacancer.com
Evan Roberts, 4023344773, eroberts@nebraskacancer.com
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Mahdi Hassan, 402-559-1947, mhassan@unmc.edu
Monica Davis, 402-559-9466, mondavis@unmc.edu
- Recruiting
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Jimar Hill, 215 349 8245, Jimar.Hill@pennmedicine.upenn.edu
- Recruiting
Mayo Clinic Hospital
Phoenix, Arizona, 85054
855-776-0015, mayocliniccancerstudies@mayo.edu
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
855-776-0015, mayocliniccancerstudies@mayo.edu
- Recruiting
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
Susan Sharry, (801) 585-3453, (Susan.Sharry@hci.utah.edu)
- Recruiting
HonorHealth Research Institute
Scottsdale, Arizona, 85258
Andrea House, 480-323-1364, ahouse@honorhealth.com
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Matt Sherman, 206-606-6347, mfsherman@fredhutch.org
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Nilufar Aliyeva, 813.745.4436, Nilufar.Aliyeva@moffitt.org
- Recruiting
The University of Kansas Clinical Research Center
Westwood, Kansas, 66205
913-945-7552, CTNurseNav@kumc.edu
About this study
Official title: A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
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:
Read more
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
Subprotocol G: RMC-9805 + cetuximab + FOLFIRI
Read the 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. Subprotocol G is an open-label, multicenter study of RMC-9805 with cetuximab and FOLFIRI in patients with previously treated, RAS G12D-mutated metastatic colorectal cancer.
- Conditions
- Colorectal Cancer, CRC, Pancreatic Ductal Adenocarcinoma, PDAC, Gastrointestinal Cancer, Metastatic Pancreatic Ductal Adenocarcinoma
- Being tested
- RMC-6236, mFOLFOX6 regimen, bevacizumab, mFOLFIRINOX regimen, cetuximab
- Keywords
- CRC, PDAC, RAS Mutation, KRAS G12X, Colorectal Cancer, Pancreatic Cancer, Pancreatic Ductal Carcinoma, KRAS Q61 Mutation, KRAS G12 Mutation, RAS Wild-type, RAS G12D Mutation
- Medical subject headings
- Colorectal Neoplasms, Gastrointestinal Neoplasms, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RMC-6236Drug
Oral tablet
mFOLFOX6 regimenDrug
IV infusion
bevacizumabDrug
IV infusion
mFOLFIRINOX regimenDrug
IV infusion
cetuximabDrug
IV infusion
gemcitabineDrug
IV infusion
nab-paclitaxelDrug
IV infusion
RMC-9805Drug
Oral Tablet
FOLFIRI regimenDrug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC | Experimental | RMC-6236 (QD) and bevacizumab with 5-fluorouracil-based regimens Receives: Drug: RMC-6236; Drug: mFOLFOX6 regimen; Drug: bevacizumab; Drug: mFOLFIRINOX regimen |
| Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC | Experimental | RMC-6236 (QD) and cetuximab with or without mFOLFOX6 Receives: Drug: RMC-6236; Drug: mFOLFOX6 regimen; Drug: cetuximab |
| Subprotocol C: metastatic PDAC | Experimental | RMC-6236 (QD) and gemcitabine with nab-paclitaxel Receives: Drug: RMC-6236; Drug: gemcitabine; Drug: nab-paclitaxel |
| Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC | Experimental | RMC-9805 (QD or BID) with or without RMC-6236 (QD), and bevacizumab with 5-fluorouracil- based regimens Receives: Drug: RMC-6236; Drug: mFOLFOX6 regimen; Drug: bevacizumab; Drug: mFOLFIRINOX regimen; Drug: RMC-9805 |
| Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC | Experimental | RMC-9805 (QD or BID) with or without RMC-6236 (QD), and cetuximab with or without mFOLFOX6 Receives: Drug: RMC-6236; Drug: mFOLFOX6 regimen; Drug: cetuximab; Drug: RMC-9805 |
| Subprotocol F: RAS G12D-mutated metastatic PDAC | Experimental | RMC-9805 (QD or BID) with or without RMC-6236 (QD), and gemcitabine with nab-paclitaxel Receives: Drug: RMC-6236; Drug: gemcitabine; Drug: nab-paclitaxel; Drug: RMC-9805 |
| Subprotocol G: RAS G12D-mutated metastatic CRC | Experimental | RMC-9805 (QD) and cetuximab with FOLFIRI Receives: Drug: cetuximab; Drug: RMC-9805; Drug: FOLFIRI regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (Subprotocols A-F)
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.
Measured: Up to 3 years
Dose limiting toxicities (Subprotocols A-F)
Number of participants with dose limiting toxicities
Measured: 28 days
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by Blinded Independent Central Review (BICR)(Subprotocol G)
Measured: Up to 3 years
Secondary outcomes (11)
Pharmacokinetics of RMC-6236 (Subprotocols A-F)
Blood concentration of RMC-6236 over time
Measured: 21 weeks
Pharmacokinetics of RMC-9805 (Subprotocols D-G)
Blood concentration of RMC-9805 over time
Measured: 21 weeks
ORR assessed by Investigator (Subprotocols A-G)
Overall Response Rate per RECIST v1.1
Measured: Up to 3 years
DOR (Subprotocols A-G)
Duration of Response per RECIST v1.1
Measured: Up to 3 years
DCR (Subprotocols A-G)
Incidence of Response per RECIST v1.1
Measured: Up to 3 years
TTR (Subprotocols A-G)
Time to Response per RECIST v1.1
Measured: Up to 3 years
PFS (Subprotocols A-G)
Progression Free Survival per RECIST v1.1
Measured: Up to 3 years
PFS Rate at 6 and 12 Months (Subprotocol G)
Measured: Up to 3 years
OS (Subprotocols A-F)
Overall Survival
Measured: Up to 3 years
Overall Survival Rate at 12 Months (Subprotocol G)
Measured: Up to 3 years
Number of Participants with Adverse Events (Subprotocol G)
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start24 May 2024
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Revolution Medicines, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Revolution Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06445062
- Sponsor's protocol ID
- RMC-GI-102
- Status last verified
- Sep 2026
- First submitted
- 20 May 2024
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40056080