Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer
- Study type
- Clinical trial
- Study name
- RMC-6236-001
- Phase
- Phase 1-2
- Design
- Open-label, single-arm phase 1–2 dose-escalation and expansion study in advanced solid tumours with RAS mutations; this report focuses on patients with PDAC
- Sample size
- 168 previously treated patients with PDAC (dose 300 mg or less)
- Source
- N Engl J Med · 2026
- Trial registration
- NCT05379985
In plain words
This was the first study of the drug daraxonrasib in people with pancreatic cancer. Its main aim was to find the right dose and check safety. In patients who took this tablet at a dose of 300 mg daily after their first treatment, the tumour shrank in about a third of them and median survival was about 13 months. Common side effects were skin rash, diarrhoea, nausea and mouth sores. These encouraging results led to a large phase 3 study (RASolute 302), which confirmed a survival benefit.
Key results
Treatment arms and regimens
Daraxonrasib (RMC-6236) orally once daily at doses of 10 to 400 mg in the dose-escalation phase; 300 mg once daily was selected as the phase 3 dose.
Source of the regimen details: Abstract of the NEJM 2026 paper (doses of 10 to 400 mg once daily; 300 mg the phase 3 dose)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
- Previously treated patients with advanced pancreatic ductal adenocarcinoma (PDAC) with an activating RAS mutation (a mutation in KRAS, NRAS or HRAS at codon 12, 13 or 61).
- ECOG performance status 0 or 1 and adequate organ function (according to ClinicalTrials.gov).
Endpoints
Primary endpoint: safety.
Secondary endpoints: pharmacokinetics and antitumour activity (objective response, duration of response, progression-free survival and overall survival).
Safety and side effects
In 168 patients with PDAC who received daraxonrasib at a dose of 300 mg or less, treatment-related adverse events of any grade were reported in 96% and grade 3 or higher adverse events in 30%. Treatment-related adverse events in at least 10% of patients included rash, diarrhoea, nausea, stomatitis or mucositis, vomiting and fatigue.
Clinical significance and place in guidelines
This study established 300 mg once daily as the phase 3 dose and was the basis for the design of the RASolute 302 trial. Based on the results of RASolute 302, on 26 August 2026 the FDA approved daraxonrasib (RASONQUE) for metastatic pancreatic adenocarcinoma after at least one previous systemic therapy or in patients who are not candidates for multi-agent therapy (FDA announcement). NCCN (version 4.2026) has reviewed the results of this study in its section on emerging therapies.
Limitations
The study was single-arm with no control group, and the efficacy subgroups were small (26 and 38 patients), so the survival data cannot be compared directly with chemotherapy. Patients were treated at different doses. Definitive evidence of efficacy came from the randomised RASolute 302 trial.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.