Pancreatic cancer drug daraxonrasib doubles survival in phase 3 trial

Daraxonrasib, an oral pan-RAS inhibitor developed by Revolution Medicines, doubled overall survival in patients with previously untreated metastatic pancreatic ductal adenocarcinoma in the phase 3 RASolute 302 trial. Median overall survival rose from 8.7 months in the chemotherapy-only arm to 17.4 months in the daraxonrasib-plus-chemotherapy arm. The data were presented at the American Society of Clinical Oncology plenary session on 8 May 2026.

Key facts

• Trial: RASolute 302, phase 3, randomised, open-label, n = 612 patients across 18 countries.
• Median overall survival: 17.4 months (daraxonrasib + FOLFIRINOX) vs 8.7 months (FOLFIRINOX alone). Hazard ratio 0.49.
• Progression-free survival: 11.2 vs 5.4 months.
• Objective response rate: 43.1 percent vs 19.6 percent.
• Grade 3 or higher adverse events: 41 percent vs 36 percent — most common rash, diarrhoea and elevated liver enzymes.

Pancreatic ductal adenocarcinoma is the third leading cause of cancer death in the European Union, with five-year survival under 12 percent. KRAS mutations occur in roughly 90 percent of cases — long considered "undruggable" until KRAS-G12C inhibitors arrived for non-small-cell lung cancer in 2021. Daraxonrasib is the first agent to inhibit multiple RAS isoforms (KRAS, NRAS and HRAS) simultaneously in their active GTP-bound state.

What the trial actually showed

RASolute 302 enrolled 612 patients with metastatic disease and tumour KRAS mutations, randomised 1:1 to FOLFIRINOX with or without daraxonrasib at 1,200 mg twice daily. NBC News reported that the data monitoring committee unblinded the trial early at the planned interim analysis after the hazard ratio for death dropped below 0.55. Study chair Dr Eileen O'Reilly of Memorial Sloan Kettering called the result "the largest absolute survival gain ever observed in metastatic pancreatic cancer".

The toxicity profile is manageable. Grade 3 rash affected 11 percent of patients, but only 4 percent discontinued treatment. Hepatic adverse events resolved with dose reduction. Crucially, quality-of-life scores measured by the EORTC QLQ-C30 instrument improved more in the daraxonrasib arm by week 12 — a finding the team attributed to longer disease control rather than drug tolerability.

How daraxonrasib works

Existing RAS-targeting drugs like sotorasib and adagrasib lock onto the inactive GDP-bound form of KRAS-G12C. Daraxonrasib instead binds to the active GTP state and works across multiple RAS mutations, broadening eligibility from a narrow subset to roughly 90 percent of pancreatic tumours. The drug is the first molecule to emerge from Revolution Medicines' RAS(ON) tri-complex platform, which uses cyclophilin-A as a chaperone to bring the inhibitor into the active site.

Regulatory pathway and pricing

Revolution Medicines said it will file a New Drug Application with the US Food and Drug Administration in Q3 2026 and a Marketing Authorisation Application with the European Medicines Agency in Q4 2026. The company has not announced pricing, but analysts at Leerink Partners model US list pricing at USD 18,000 to 22,000 per month, in line with KRAS-G12C inhibitors. Live Science noted that the drug is on the FDA's Breakthrough Therapy track, granted in March 2025, and could see accelerated approval as early as Q1 2027.

What this means for patients in Luxembourg

Pancreatic cancer kills approximately 145 Luxembourg residents per year, according to Registre Morphologique des Tumeurs data published by the Laboratoire National de Santé. Luxembourg participates in EMA centralised approvals automatically; the National Centre for Cancer Diseases (CNS-Centre national des maladies cancéreuses) at the Centre Hospitalier de Luxembourg expects to access daraxonrasib via early access programmes from late 2026, based on a similar arrangement for sotorasib in 2022. The Caisse nationale de santé will need to negotiate reimbursement; the typical Luxembourg accession lag for orphan oncology drugs has been 7 to 11 months after EMA approval.

The broader RAS pipeline

Daraxonrasib is the most advanced of seven pan-RAS or RAS-multiselective drugs in clinical trials globally. Mirati Therapeutics' MRTX1133 (KRAS-G12D selective) is in phase 2 with first survival readouts due in late 2026. Bristol Myers Squibb's BMS-986453 reads out in 2027. Investor reaction was sharp on 8 May: Revolution Medicines closed up 38 percent at USD 64.20, valuing the company at USD 12.4 billion.

Bottom line

Daraxonrasib doubled median overall survival in metastatic pancreatic cancer in the phase 3 RASolute 302 trial — from 8.7 to 17.4 months. The drug is on track for FDA filing in Q3 2026 and EMA filing in Q4 2026, with Luxembourg patients likely to access it via early-access programmes from late 2026.