Clinical trialPhase 3Pancreatic cancer

Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

N Engl J Med · 2026500 patients

O'Reilly EM, Wainberg ZA, Hendifar AE, Borad MJ, Pietrantonio F, Pant S, et al. N Engl J Med. 2026. 395:325-337

Study type: Clinical trial
Study name: RASolute 302
Phase: Phase 3
Design: International, randomised, open-label trial
Sample size: 500 patients
Source: N Engl J Med · 2026
Trial registration: NCT06625320

In plain words

This large study showed that a daily tablet called daraxonrasib, in patients whose pancreatic cancer had spread and grown after the first treatment, raised the average survival from about 6 and a half months to more than 13 months, and it caused fewer severe side effects than chemotherapy.

Key results

13.2 vs 6.6 months

Median overall survival (RAS G12)

HR 0.40; P<0.001

13.2 vs 6.7 months

Median overall survival (overall population)

HR 0.40; P<0.001

7.3 vs 3.5 months

Median progression-free survival (RAS G12)

HR 0.45; P<0.001

7.2 vs 3.6 months

Median progression-free survival (overall population)

HR 0.49; P<0.001

61.8% vs 69.6%

Grade 3 or higher adverse events

Drugs in this study:Fluorouracil (5-FU)Gemcitabine (Gemzar)Irinotecan (Camptosar)Paclitaxel (Taxol)

Dose and schedule cards

Daraxonrasib (RASolute 302)

Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or patients unfit for multiagent therapy (FDA label); ESMO: RAS G12 mutation and ECOG 0–1Cycle length: ContinuousOn the page “Pancreatic cancer” · Metastatic disease: first-line, maintenance and later lines

Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or patients unfit for multiagent therapy (FDA label); ESMO: RAS G12 mutation and ECOG 0–1

Drug	Dose	Route	Schedule
Daraxonrasib	300 mg once daily	Oral	Continuous

Cycle length: Continuous
Duration: Until disease progression or unacceptable toxicity

Dose from the FDA label; evidence: RASolute 302.

Skin toxicity prevention from the start of treatment: a topical corticosteroid and a moisturizing cream on the face and chest, limiting sun exposure and using sunscreen with SPF 30 or higher, and considering prophylactic oral doxycycline or minocycline. Dose reduction to 200 mg, then to 150 mg; discontinue if 150 mg is not tolerated; grade 3 rash, stomatitis or diarrhoea → withhold until grade ≤1, then resume at a lower dose.

On the page “Pancreatic cancer” · Metastatic disease: first-line, maintenance and later lines

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.

Treatment arms and regimens

1Daraxonrasib (248 patients)

Daraxonrasib 300 mg orally once daily (continuous), until disease progression or unacceptable toxicity. Per the FDA label, prophylaxis of skin toxicity is recommended from the start of treatment (topical corticosteroid and emollient on the face and chest, sunscreen, and consideration of oral doxycycline or minocycline); dose reduction to 200 and then 150 mg.

2Physician's choice chemotherapy (252 patients)

Standard chemotherapy of the physician's choice: mFOLFIRINOX, gemcitabine + nab-paclitaxel, FOLFOX or liposomal irinotecan + fluorouracil/leucovorin; until disease progression or unacceptable toxicity. Regimen doses are not stated in the available sources.

Source of the regimen details: FDA label for daraxonrasib (RASONQUE; Dosage, Clinical Studies and Adverse Reactions sections) and ClinicalTrials.gov NCT06625320; doses of the control-arm regimens are not stated in these sources

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

Patients with metastatic pancreatic adenocarcinoma with disease progression after one prior line of systemic therapy (fluoropyrimidine-‎ or gemcitabine-based regimen), ECOG 0 or 1, measurable disease (RECIST 1.1) and known RAS mutation status (mutant or wild-type) on local testing. Per the FDA label, 92% had a KRAS G12 mutation, 5% a KRAS mutation at other sites (G13 and Q61) and 3% no identified RAS mutation; median age 66 years, and 70% had liver metastases.

Endpoints

Dual primary outcomes: overall survival and progression-free survival in the RAS G12 population. Key secondary outcomes: overall survival and progression-free survival in the overall population, objective response and patient-reported quality of life; safety.

Safety and side effects

Treatment-emergent adverse events were reported in all patients in the daraxonrasib group and 97.7% of the chemotherapy group; grade 3 or higher adverse events 61.8% versus 69.6%. Discontinuation due to treatment-related adverse events occurred in 1.2% of the daraxonrasib group and 11.2% of the chemotherapy group (abstract).

Per the FDA label: the most common adverse reactions (≥20%) were rash, diarrhoea, stomatitis, nausea, fatigue, vomiting, abdominal pain, oedema, decreased appetite and haemorrhage. Serious adverse reactions in 30%, dose interruption due to adverse reactions in 69% (especially rash 27% and stomatitis 20%), dose reduction in 37% (rash 18%) and permanent discontinuation in 2.9%. Important warnings: skin toxicity, stomatitis, diarrhoea, gastrointestinal perforation and interstitial lung disease.

Clinical significance and place in guidelines

The first positive phase 3 trial of a RAS inhibitor in pancreatic cancer. Based on this study, on 26 August 2026 the FDA approved daraxonrasib for metastatic pancreatic adenocarcinoma after at least one prior systemic therapy or for patients unsuitable for multi-agent therapy, without restriction to a specific mutation.

Limitations

Open-label design; patients with good performance status; relatively short follow-up; small number of patients without a G12 mutation.

Original article (DOI)PubMed ClinicalTrials.gov

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.