Early Trial Supports Phase III Evaluation of Daraxonrasib in RAS-Mutant NSCLC
By: Julia Cipriano, MS, CMPP
Posted: Monday, September 14, 2026
The oral RAS(ON) multiselective inhibitor daraxonrasib showed antitumor activity in pretreated patients with RAS-mutant non–small cell lung cancer (NSCLC), according to results from the multicenter phase I/II RMC-6236-001 trial published in The New England Journal of Medicine. David S. Hong, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues reported a favorable benefit-risk profile.
“The results are notable in a treatment landscape characterized by limited options with modest clinical benefit and substantial toxic effects,” the investigators commented. “[They] highlight the therapeutic potential of RAS(ON) multiselective inhibition.”
In this dose-escalation and -expansion study, patients with previously treated advanced RAS-mutant NSCLC received daraxonrasib at doses ranging from 10 to 400 mg once daily in 21-day cycles. As of the data cutoff, 136 patients who were administered doses of 300 mg or less had been evaluated for safety and efficacy.
Objective responses were observed in 31% of patients receiving daraxonrasib at doses of 120 mg or less, 34% of those receiving 160 to 220 mg, and 37% of those receiving 300 mg. Adverse events of any grade, regardless of attribution, occurred in 99% of patients treated with a dose of 300 mg or less; rash, diarrhea, nausea, vomiting, and mucositis or stomatitis were each reported in at least 30%. Grade 3 or higher adverse events were documented in 54% of patients, with pneumonia (10%), diarrhea (9%), rash (8%), and anemia (5%) occurring in at least 5%. There were four grade 5 adverse events.
“These data support the ongoing phase III randomized RASolve 301 trial of second-line daraxonrasib as compared with docetaxel in patients with RAS-mutant NSCLC,” the investigators wrote, noting that 200 mg was selected.
Disclosure: For full disclosures of the study authors, visit nejm.org.
