Review articlePancreatic cancer

Daraxonrasib: The first-in-class RAS(ON) multi-selective inhibitor approved for treatment of metastatic pancreatic adenocarcinoma

DD&T · 2026500 patients (the RASolute 302 trial reported in this review)

Sun Y, Pang C, Gao J. DD&T. 2026

Study type: Review article
Study name: RASolute 302
Design: Narrative review of daraxonrasib and the randomised phase 3 RASolute 302 trial
Sample size: 500 patients (the RASolute 302 trial reported in this review)
Source: DD&T · 2026

In plain words

Daraxonrasib is a new oral drug that blocks the RAS signalling pathway, which plays an important role in pancreatic cancer. According to this review, in people with advanced pancreatic cancer who had already been treated, this drug increased median survival from 6.7 to 13.2 months compared with chemotherapy. Side effects such as rash, diarrhoea and mouth sores were common, and one death from pneumonitis (lung inflammation) was reported. The decision to use this drug should be made with the treating doctor, based on the patient's general condition.

Key results

13.2 vs 6.7 months

Median overall survival (whole randomised population)

HR 0.40

7.2 vs 3.6 months

Median progression-free survival

Whole randomised population

43.6% vs 57.5%

Grade 3 or higher treatment-related adverse events

Daraxonrasib vs chemotherapy

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

Oral, non-covalent, multi-selective RAS(ON) inhibitor. Dosing details in the full text.

2Chemotherapy (comparator)

The type and dose of chemotherapy drugs are not given in the abstract. Dosing details in the full text.

Source of the regimen details: Abstract of the paper; doses are not given in the abstract and dosing details should be checked in the full text

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

According to the abstract, RASolute 302 enrolled previously treated patients with good performance status. The FDA approval covers adults with metastatic pancreatic adenocarcinoma who have received prior systemic therapy or are not candidates for multi-agent systemic therapy. The approval is not restricted to a specific mutation.

Endpoints

The abstract does not explicitly define primary and secondary endpoints. Reported results include median overall survival, progression-free survival and grade 3 or higher treatment-related adverse events.

Safety and side effects

Grade 3 or higher treatment-related adverse events were less frequent with daraxonrasib than with chemotherapy (43.6% versus 57.5%). However, one treatment-related death from pneumonitis occurred. Common toxicities included rash, diarrhoea and stomatitis.

Clinical significance and place in guidelines

According to the abstract, the FDA has approved daraxonrasib for adults with metastatic pancreatic adenocarcinoma who have received prior systemic therapy or are not candidates for multi-agent systemic therapy. The approval is not restricted to a specific mutation. The marked survival improvement in previously treated patients makes this drug an important option in this group. Its status in clinical guidelines (such as NCCN and ESMO) should be checked separately, as the abstract does not address them.

Limitations

According to the authors, limited follow-up and the small size of the non-G12 subgroups call for caution in generalising the trial results. Acquired resistance, often associated with reactivation of the RAS pathway, is a major challenge. Safety and long-term outcomes in patients with poorer performance status also need further study. This is a review article and does not report primary trial data.

Original article (DOI)PubMed

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.