The news at a glance
- Daraxonrasib is a tablet that switches off the faulty RAS protein; this protein is faulty in more than 9 in 10 people with pancreatic cancer [1].
- In patients whose disease had grown after their first chemotherapy, this tablet almost doubled survival: patients typically lived more than a year, compared with about 7 months with chemotherapy [1].
- Serious side effects were less common with this tablet than with chemotherapy [1].
- The drug was approved in the United States in August 2026 [4].
- Overall survival: how long patients lived.
- Progression-free survival: how long the disease did not get worse.
- Disease-free or event-free survival: how long the disease did not come back after treatment.
- Median: the number that half of patients were above and half below; for example, "a median of 10 months" means that in half of patients the disease stayed under control for at least 10 months.
- Phase 3: a large, careful study comparing a new drug with the usual treatment; the basis of most approvals.
Talk to your doctor about what this result means for you.
What was reported?
For physicians
For decades the RAS protein was called an "undruggable target". Abnormal activation of the RAS pathway is the main driver of pancreatic cancer, and mutations in this gene are found in more than 90% of cases [1]. Daraxonrasib (formerly RMC-6236) is an oral "RAS(ON)" inhibitor that blocks the active, GTP-bound form of the RAS protein, whether mutant or wild-type [1, 3].
In the international phase 3 RASolute 302 trial, 500 patients with previously treated metastatic pancreatic cancer were randomised to daraxonrasib (248 patients) or chemotherapy of the physician's choice (252 patients); 91.8% of patients had a RAS G12 mutation [1]. Median overall survival was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and median progression-free survival was 7.3 vs 3.5 months [1]. Results were similar in the overall study population, including patients in whom no RAS mutation was identified (overall survival 13.2 vs 6.7 months) [1].
These results followed promising phase 1 and 2 data in which, among 26 patients with a RAS G12 mutation who received daraxonrasib as second-line treatment at a dose of 300 mg, an objective response was seen in 35% [2].
What does this finding mean for patients?
If you or someone you love has pancreatic cancer that has spread, and the disease has grown after the first chemotherapy, this is the first time a targeted tablet has almost doubled survival in a direct comparison with chemotherapy [1]. The drug has been approved in the United States [4]. Talk to your treating doctor about whether it suits your situation (including your general physical condition).
Trial details and regimen (for physicians)
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- The dual primary endpoints (overall survival and progression-free survival) were assessed in the RAS G12 population; the hazard ratio for overall survival in the overall population was also 0.40, and the hazard ratio for progression-free survival in the overall population was 0.49 [1].
- Common adverse events include rash, diarrhoea, nausea and stomatitis [2]; pneumonitis has also been reported [4].
- The FDA label is not restricted to a specific RAS mutation and also covers patients unsuitable for multi-agent chemotherapy; this label is broader than the trial population and is a matter of debate [4, 5].
- Trial patients had good performance status and follow-up is still limited; acquired resistance, often through reactivation of the RAS pathway, is the next major challenge [4].
Daraxonrasib dose and schedule (FDA label)
Daraxonrasib monotherapy
Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or patients who are not candidates for multi-agent therapyCycle length: Daily, continuous
Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or patients who are not candidates for multi-agent therapy
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Daraxonrasib | 300 mg (100 mg and 150 mg tablets) | Oral, with or without food; swallow tablets whole | Once daily, at the same time each day |
Skin prophylaxis from the start of treatment: a topical corticosteroid on the face and chest and an emollient cream; limit sun exposure and use sunscreen with SPF 30 or higher; consider a prophylactic oral antibiotic (such as doxycycline or minocycline). Missed dose: skip it if more than 4 hours have passed; do not take an extra dose after vomiting. Dose levels: 300 → 200 → 150 mg; unable to tolerate 150 mg: discontinue. Grade 2 rash, stomatitis or diarrhoea: consider withholding until grade 1, then resume at the same dose or the next lower level; grade 3: withhold until grade 1 and resume at the next lower level; grade 4: discontinue permanently. Grade 2 ILD/pneumonitis: withhold until grade 1 and, if appropriate, resume at the next lower level; recurrent grade 2 or grade 3 to 4: discontinue permanently. Grade 4 gastrointestinal perforation: discontinue permanently. Interactions: strong CYP3A inhibitors that also inhibit P-gp, and ciclosporin: avoid. Strong CYP3A inhibitor without P-gp inhibition, or a P-gp inhibitor: 150 mg; moderate CYP3A inhibitor with P-gp inhibition: 100 mg; without P-gp inhibition: 200 mg. Strong CYP3A inducer (if unavoidable) or moderate CYP3A inducer: 400 mg. Separate P-gp substrates by at least 4 hours. Contraception until 1 week after the last dose [7].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Approval status, limitations and next steps
- This tablet is approved in the United States for pancreatic cancer that has spread, for patients who have had at least one previous treatment [4].
- In this study, patients and doctors knew which treatment was being given, and some groups of patients were small; so the result is not certain for all patients [1, 4].
- It is not yet known how much this tablet helps as a first treatment or together with chemotherapy [4, 6].
- Approval: on 26 August 2026 the FDA approved daraxonrasib for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multi-agent therapy [4] (FDA announcement).
- The study was open-label and the subgroups without G12 mutations were small; the results should be generalised to all patients with caution [1, 4].
- The role of this drug in first-line treatment and in combination with chemotherapy is still being studied [4, 6].
Experts see these results as the start of the era of RAS-targeted therapy in pancreatic cancer, and inhibitors specific to mutations such as G12D are also being evaluated [6].
Main studies
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Key studies
2 itemsDaraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer
Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer
References
7 referencesShow all references, 6 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer
- 3Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy
- 4
- 5An imprecise label in the era of precision medicine: labelling and access for daraxonrasib, the first pan-RAS inhibitor approval
- 6
- 7RASONQUE (daraxonrasib) tablets, for oral use: Prescribing Information
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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