# Daraxonrasib shows activity in RAS-mutant lung cancer > In an early, single-group study, tumor responses occurred in 31% to 37% across dose ranges, while 54% of 136 evaluated patients had grade 3 or worse adverse events. _Source: NEJM paper, PubMed, ClinicalTrials.gov, Crossref and OpenAlex · 2026-09-24 · 7 min read · Verified against primary sources_ Canonical: https://iyu.app/e/daraxonrasib-ras-mutant-nsclc-phase-1-2 ## The 60-second version Daraxonrasib produced objective responses in 31% to 37% of dose groups in an early study of previously treated RAS-mutant NSCLC. **Key points** - The analysis included 136 patients receiving daily doses of 300 mg or less. - Grade 3 or higher adverse events occurred in 54%, and four grade 5 events were reported. - The open-label, single-group phase 1–2 design had safety as its primary endpoint. - A randomized phase 3 comparison with docetaxel is needed to test clinical benefit against standard care. **Verdict.** The drug showed antitumor activity worth testing, but response rate alone does not establish longer survival or a new standard of care. ## Full explainer > **⚑ Caveat:** This was an open-label, single-group phase 1–2 study funded by Revolution Medicines. It can establish safety findings and an antitumor signal, but it cannot prove a survival benefit or superiority to standard treatment. ### The result — Tumor responses rose across tested dose ranges Daraxonrasib, also called RMC-6236, was tested in people with previously treated advanced RAS-mutant non-small-cell lung cancer. Among 136 patients evaluated at daily doses of 300 mg or less, investigator-assessed objective response rates ranged from 31% to 37% across dose groups. - **136** — patients evaluated at doses of 300 mg or less - **31–37%** — objective response across the reported dose groups - **54%** — patients with grade 3 or higher adverse events - **≤120 mg daily:** 31% had an investigator-assessed objective response. - **160–220 mg daily:** 34% had an investigator-assessed objective response. - **300 mg daily:** 37% had an investigator-assessed objective response. An objective response means imaging met standardized criteria for complete or partial tumor shrinkage. It does **not** by itself show that patients lived longer, had better quality of life, or did better than patients receiving another treatment. ### The design — What phase 1–2 can and cannot answer The multicenter trial escalated and expanded doses from 10 to 400 mg, given orally once daily in 21-day cycles. Safety was the primary endpoint. Objective response and duration of response were secondary endpoints assessed by investigators using RECIST 1.1. The trial was open-label and single-group. Without random assignment to an active comparator, the response rate cannot establish that daraxonrasib outperforms standard care. It also leaves overall survival and patient-reported benefit unresolved. ### Safety — Severe adverse events were common Any-grade adverse events, regardless of attribution, were reported in 99% of patients. Rash, diarrhea, nausea, vomiting, and mucositis or stomatitis each occurred in at least 30%. Grade 3 or higher events occurred in 54%, and four grade 5 events were reported. - **Pneumonia:** Grade 3 or higher in 10% of patients. - **Diarrhea:** Grade 3 or higher in 9% of patients. - **Rash:** Grade 3 or higher in 8% of patients. - **Anemia:** Grade 3 or higher in 5% of patients. > **i** The abstract reports adverse events regardless of attribution. Four grade 5 events occurred, but the abstract alone does not establish that daraxonrasib caused each fatal event. ### The mechanism — A broader way to inhibit active RAS Daraxonrasib is designed as a RAS(ON) multiselective tri-complex inhibitor. It targets the active, GTP-bound state across mutant and wild-type RAS isoforms, rather than one mutation alone. The broad reach is the scientific attraction; dose selection and effects on normal RAS signaling are part of the safety question. ### Evidence ownership — Funding and comparison matter Revolution Medicines funded the study, and several authors were company employees. That does not negate the measurements, but it strengthens the need for mature follow-up and randomized independent comparison. The phase 3 RASolve 301 trial is recruiting and plans to compare daraxonrasib with docetaxel in previously treated RAS-mutant NSCLC. Its comparative outcomes will be more informative for treatment decisions than response rate alone. > Tumor shrinkage is a reason to run the definitive trial, not a substitute for one. ### Practical meaning — The signal is promising, the standard is not settled The study supports further testing across RAS mutations while leaving the best dose, comparative benefit, long-term safety and survival effect open. Treatment decisions remain individualized and should be made with an oncology team, not from a response-rate headline. ## Primary sources - [Telegram post 1503](https://t.me/CNSmydream/1503) - [NEJM paper (DOI)](https://doi.org/10.1056/NEJMoa2504059) - [PubMed record 42685317](https://pubmed.ncbi.nlm.nih.gov/42685317/) - [ClinicalTrials.gov NCT05379985](https://clinicaltrials.gov/study/NCT05379985) - [Crossref metadata](https://api.crossref.org/works/10.1056%2FNEJMoa2504059) - [OpenAlex record](https://openalex.org/W7206171580) --- _Published by iyu (https://iyu.app) — the day's AI news, checked against primary sources and rewritten in plain language. Free to quote with attribution and a link to the canonical URL._