RMC-6236-001 (NSCLC) Key Takeaways
Design — Phase 1–2 multicenter dose-escalation/expansion; daraxonrasib 10–400 mg orally once daily, 21-day cycles; primary endpoint safety. (NEJM, DCO 21-Jul-2025)
Population — Previously treated advanced RAS-mutant (non-G12C) NSCLC after platinum chemotherapy and anti-PD-(L)1; n=136 at ≤300 mg. (NEJM)
ORR — Dose-dependent: 31% (≤120 mg), 34% (160–220 mg), 37% (300 mg); docetaxel-naïve 160–220 mg subgroup (n=38): confirmed ORR 42%, DCR 89%. (NEJM / RevMed PR)
Survival — Docetaxel-naïve 160–220 mg subgroup: median PFS 8.3 mo (95% CI 4.0–12.5), median OS 16.0 mo (9.5–NE). (NEJM Fig 2 / RevMed PR)
Safety — Any-grade AEs 99% (any attribution); grade ≥3 AEs 54% (pneumonia 10%, diarrhea 9%, rash 8%, anemia 5%); four grade 5 events. At 160–220 mg: grade 3 TRAEs 25%, no grade 4/5 TRAEs. (NEJM)
Regulatory — ⚠️ Investigational in NSCLC. ✅ FDA-approved (Aug 2026, as RASONQUE) only in metastatic pancreatic adenocarcinoma. Phase 3 RASolve 301 vs docetaxel ongoing (NCT06881784). (RevMed)
Sponsor / Drug — Revolution Medicines; daraxonrasib (RMC-6236), an oral RAS(ON) multi-selective, noncovalent tri-complex inhibitor. (RevMed)
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated September 2, 2026.
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Top KOLs Discussing Daraxonrasib in NSCLC
RMC-6236-001 Key Slides & Visuals
| Population (docetaxel-naïve, 160–220 mg) | N | Median PFS (95% CI) | Median OS (95% CI) |
|---|---|---|---|
| RAS G12 mutations | 33 | 8.3 mo (4.5–13.3) | — |
| Any RAS mutation | 38 | 8.3 mo (4.0–12.5) | 16.0 mo (9.5–NE) |
PFS medians per NEJM Figure 2 (data cutoff Jul 21, 2025); OS per Revolution Medicines release (Sept 2, 2026). Values read from the published figure — no interpolation.
Daraxonrasib NSCLC Top Tweets
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About the RMC-6236-001 Trial (NSCLC Cohort)
RMC-6236-001 (NCT05379985) is the first-in-human Phase 1–2 study of daraxonrasib, an oral RAS(ON) multi-selective, noncovalent tri-complex inhibitor that targets GTP-bound mutant and wild-type RAS isoforms. RAS mutations are the most common oncogenic drivers in NSCLC, occurring in roughly 30% of cases; outside RAS G12C there are no approved targeted therapies. The NSCLC results, published in the New England Journal of Medicine on September 2, 2026 (Arbour et al., NEJM 2026;395:882-893), cover 136 previously treated patients with advanced RAS-mutant (non-G12C) disease whose cancer progressed on or after platinum-based chemotherapy and anti-PD-(L)1 therapy.
✅ Daraxonrasib is FDA-approved (August 2026, brand name RASONQUE) for metastatic pancreatic adenocarcinoma after at least one prior systemic therapy — the first broad RAS-targeted medicine approved in that disease. ⚠️ In NSCLC it remains investigational: these Phase 1–2 results informed the design of RASolve 301 (NCT06881784), the ongoing global randomized Phase 3 trial comparing daraxonrasib with docetaxel in previously treated RAS-mutant NSCLC.
Trial Methodology & Results
Study Design
Phase 1–2, multicenter, open-label dose-escalation and dose-expansion; daraxonrasib 10–400 mg orally once daily in 21-day cycles. Primary endpoint: safety.
Population
Previously treated advanced RAS-mutant (non-G12C) NSCLC after platinum-based chemotherapy and anti-PD-(L)1 therapy; 136 patients treated at ≤300 mg evaluated (DCO Jul 21, 2025).
Intervention
Daraxonrasib (RMC-6236) — oral RAS(ON) multi-selective, noncovalent tri-complex inhibitor of GTP-bound mutant and wild-type RAS.
Endpoints
Primary: safety. Secondary: investigator-assessed objective response and duration of response per RECIST 1.1.
Lead Authors
Kathryn C. Arbour, MD (MSKCC) and colleagues incl. David S. Hong, MD, for the RMC-6236-001 Investigators.
Next Step
RASolve 301 (NCT06881784): global randomized Phase 3, daraxonrasib vs docetaxel in previously treated RAS-mutant NSCLC — ongoing.
Objective Response
Responses were dose-dependent: 31% at doses of 120 mg or less, 34% at 160–220 mg, and 37% at 300 mg (NEJM, n=136, DCO 21-Jul-2025). In the docetaxel-naïve subgroup treated at 160–220 mg (n=38) — the population mirrored in the Phase 3 — confirmed ORR was 42% (95% CI 26–59) with a disease control rate of 89% (95% CI 75–97) (RevMed PR, Sept 2, 2026).
ORR 42% in the docetaxel-naïve 160–220 mg subgroupSource: NEJM (DOI 10.1056/NEJMoa2504059)
Progression-Free & Overall Survival
In the docetaxel-naïve 160–220 mg subgroup, median PFS was 8.3 months (95% CI 4.0–12.5 for any RAS mutation, n=38; 4.5–13.3 for RAS G12, n=33 — NEJM Figure 2) and median OS was 16.0 months (95% CI 9.5–NE) (RevMed PR, Sept 2, 2026). PFS and OS were not formal endpoints of this Phase 1–2 study.
Median OS 16.0 months in the docetaxel-naïve subgroupSource: Revolution Medicines (Sept 2, 2026)
Safety
Adverse events of any grade, regardless of attribution, occurred in 99% of patients at ≤300 mg; rash, diarrhea, nausea, vomiting, and mucositis/stomatitis each occurred in at least 30%. Grade ≥3 AEs occurred in 54% (pneumonia 10%, diarrhea 9%, rash 8%, anemia 5%), and four grade 5 adverse events occurred (NEJM, n=136). Within the 160–220 mg dose range, grade 3 treatment-related AEs occurred in 25% of patients (most commonly rash 8% and diarrhea 3%) with no grade 4 or 5 TRAEs (RevMed PR). Physician reaction centered on this efficacy–toxicity balance.
Grade ≥3 AEs 54% overall; G3 TRAEs 25% at 160–220 mgSource: NEJM (DOI 10.1056/NEJMoa2504059)
Daraxonrasib NSCLC in the News
Daraxonrasib NSCLC FAQ
What did the RMC-6236-001 trial show for daraxonrasib in NSCLC?
In the Phase 1-2 RMC-6236-001 study published in NEJM (Sept 2, 2026), daraxonrasib produced dose-dependent objective responses in previously treated RAS-mutant (non-G12C) NSCLC: 31% at doses of 120 mg or less, 34% at 160-220 mg, and 37% at 300 mg (data cutoff July 21, 2025; n=136). In a docetaxel-naive subgroup treated at 160-220 mg (n=38), confirmed ORR was 42% with a disease control rate of 89%.
Is daraxonrasib (RASONQUE) FDA-approved for lung cancer?
No. Daraxonrasib is investigational in NSCLC. Its FDA approval (August 2026, brand name RASONQUE) covers metastatic pancreatic adenocarcinoma after at least one prior systemic therapy. Approval in lung cancer would depend on the ongoing Phase 3 RASolve 301 trial.
What survival outcomes were reported?
In the docetaxel-naive 160-220 mg subgroup (n=38), median progression-free survival was 8.3 months (95% CI 4.0-12.5) and median overall survival was 16.0 months (95% CI 9.5-not estimable), per NEJM Figure 2 and the Revolution Medicines announcement.
What is the safety profile of daraxonrasib in NSCLC?
Per the NEJM report (n=136, doses of 300 mg or less), adverse events of any grade occurred in 99% of patients regardless of attribution; grade 3 or higher AEs occurred in 54% (pneumonia 10%, diarrhea 9%, rash 8%, anemia 5%), and four grade 5 events occurred. In the 160-220 mg dose range, grade 3 treatment-related AEs occurred in 25% with no grade 4 or 5 TRAEs.
What is the next step for daraxonrasib in RAS-mutant NSCLC?
RASolve 301 (NCT06881784), a global randomized open-label Phase 3 trial comparing daraxonrasib with docetaxel in previously treated locally advanced or metastatic RAS-mutant NSCLC, is ongoing and was designed from these Phase 1-2 results.