Clinical trial · Interventional
Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 26, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260926-000001
Summary
Brief summary (as posted)
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 Subprotocol G: RMC-9805 + cetuximab + FOLFIRI
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
| CRC | Colorectal Carcinoma | ALIAS | 0.90 |
| Gastrointestinal Cancer | Malignant Digestive System Neoplasm | ALIAS | 0.90 |
| Metastatic Pancreatic Ductal Adenocarcinoma | Pancreatic Ductal Adenocarcinoma | CURATED_BROADER | 0.78 |
| Pancreatic Ductal Adenocarcinoma | Pancreatic Ductal Adenocarcinoma | ONTOLOGY_EXACT | 0.98 |
| PDAC | Pancreatic Ductal Adenocarcinoma | ALIAS | 0.90 |
Interventions
Interventions (9)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| bevacizumab | Drug | Bevacizumab | ALIAS |
| cetuximab | Drug | Cetuximab | ALIAS |
| FOLFIRI regimen | Drug | FOLFIRI Regimen | ALIAS |
| gemcitabine | Drug | Gemcitabine | ALIAS |
| mFOLFIRINOX regimen | Drug | — | UNRESOLVED |
| mFOLFOX6 regimen | Drug | — | UNRESOLVED |
| nab-paclitaxel | Drug | Nab-paclitaxel | ALIAS |
| RMC-6236 | Drug | — | UNRESOLVED |
| RMC-9805 | Drug |
Design
Arms and outcomes
Arms (7)
- type
- EXPERIMENTAL
- label
- Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
- description
- RMC-6236 (QD) and bevacizumab with 5-fluorouracil-based regimens
- interventionNames
- Drug: RMC-6236
- Drug: mFOLFOX6 regimen
- Drug: bevacizumab
- Drug: mFOLFIRINOX regimen
- type
- EXPERIMENTAL
- label
- Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
- description
- RMC-6236 (QD) and cetuximab with or without mFOLFOX6
- interventionNames
- Drug: RMC-6236
- Drug: mFOLFOX6 regimen
- Drug: cetuximab
- type
- EXPERIMENTAL
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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, C and G) * Presence of RAS G12D mutation (Subprotocol D, E, F, G) 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.
References
Publications (1)
- DERIVEDCregg 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 40056080