Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC

Phase 1/2 Recruiting 616 enrolled Revolution Medicines, Inc.

Non-randomizedParallel-groupOpen-labelTreatment

Summary

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other. The first four subprotocols include the following: Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805

Timeline

Start: 2024-01-18
Primary completion: 2027-06
Completion: 2028-12

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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Elironrasib	Unknown	—	Oral
Subject	RMC-9805	Unknown	—	Oral
Subject	daraxonrasib	Small molecule	—	Oral
Background	Carboplatin	Small molecule	—	Intravenous
Background	Cisplatin	Other / unclassified	—	Intravenous
Background	Pembrolizumab	Monoclonal antibody	—	Intravenous
Background	Pemetrexed	Small molecule	—	Intravenous

Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC

Summary

Timeline

Publications

Drugs

Indications