EMA Recommends First RAS Inhibitor for Pancreatic Cancer

Rasonque (daraxonrasib)What to know

30-second read

For Oncology

Who

Adults with metastatic pancreatic ductal adenocarcinoma (PDAC) after at least one prior systemic therapy — over 90% of PDAC tumors carry a KRAS mutation.

What’s new

The first RAS-targeted therapy to reach regulators for pancreatic cancer: an oral pan-RAS(ON) inhibitor, FDA-approved in the US since August 2026, now EU-recommended.

Evidence

Phase 3 RASolute 302 (500 patients): median overall survival 13.2 vs 6.7 months on chemotherapy (HR 0.40); progression-free survival 7.2 vs 3.6 months.

Big advantage

Roughly doubles median survival against chemotherapy alone, in a disease where second-line options have rarely beaten chemotherapy at all.

Key consideration

Interstitial lung disease/pneumonitis in 2.4% of patients (one fatal), plus GI perforation, severe diarrhea and dermatologic toxicity need active monitoring.

Availability

US: available now, reported ~$39,800 per 30-day supply before assistance. EU: pending a European Commission decision, typically ~2 months after this opinion.

Practice impactConsider for eligible patients

A pancreatic cancer drug with a real survival benefit and a toxicity profile oncologists can actively manage, not avoid. US-approved and prescribable now; EU patients wait on the European Commission’s decision, expected within about two months.

Read the full physician analysis

Full analysis · 9 min readFDA approval notice, 26 Aug 2026 · EMA CHMP opinion, 15 Oct 2026 · RASolute 302 (Phase 3)

EMA’s Committee for Medicinal Products for Human Use recommended EU marketing authorisation on 15 October 2026 for Rasonque (daraxonrasib), an oral RAS inhibitor from Revolution Medicines, for adults with metastatic pancreatic ductal adenocarcinoma who have already had one line of systemic therapy. It is the first RAS-targeted therapy to reach a regulatory decision for pancreatic cancer anywhere — FDA approved the same drug, for the same population, in the US on 26 August 2026, making it available to American oncologists for nearly two months already. For a cancer in which more than 90% of tumors carry a RAS mutation and prior RAS-targeted drugs covered almost none of them, this is less an incremental addition to the regimen list than a genuinely new mechanism entering practice.

Why RAS inhibition matters specifically here

Pancreatic ductal adenocarcinoma is defined, more than almost any other solid tumor, by a single gene family: KRAS mutations appear in upwards of 90% of cases, concentrated at codon 12, with G12D the single most common variant (roughly a third of cases in published cohorts) and G12V close behind. That made RAS an obvious oncology target for decades — and, for just as long, one the field could not drug directly, because RAS proteins lack an obvious pocket for a small molecule to bind. The first RAS inhibitors to reach the clinic, sotorasib and adagrasib, solved that problem narrowly: both target only the G12C mutation, which is common in lung cancer but rare in pancreatic cancer, leaving most PDAC patients with no RAS-targeted option at all. Daraxonrasib takes a different approach. Independent oncology coverage and the company describe it as forming a tri-molecular complex with the cellular protein cyclophilin A and RAS itself, locking the GTP-bound, “active” form of multiple RAS mutants — not just G12C — in a signaling-incompetent state. That broader reach is the reason this particular pancreatic cancer population, dominated by G12D and G12V, now has a RAS-targeted option at all.

What RASolute 302 actually showed

The approval and the CHMP opinion both rest on RASolute 302, a Phase 3 trial that randomized roughly 500 adults with previously treated metastatic PDAC 1:1 to daraxonrasib 300 mg orally once daily or investigator’s choice of one of four standard chemotherapy regimens. The headline result: median overall survival of 13.2 months on daraxonrasib against 6.7 months on chemotherapy, a hazard ratio of 0.40. A later ad hoc analysis reported a closer 12.4-month daraxonrasib figure against the same 6.7-month comparator (hazard ratio 0.49) — coverage of the data describes the two readouts as broadly consistent rather than contradictory, and this story discloses both rather than picking the more favorable one. Progression-free survival by blinded independent central review was 7.2 months on daraxonrasib versus 3.6 months on chemotherapy. In a disease where multiple second-line regimens have failed to clearly beat each other on survival, and where oncologists have had genuinely limited ammunition after first-line failure, a doubling of median OS against an active chemotherapy comparator — not a placebo — is a result worth treating as practice-relevant rather than merely statistically positive.

Second-line metastatic PDAC: daraxonrasib versus chemotherapy

	Daraxonrasib (Rasonque)	Investigator's-choice chemotherapy
Mechanism	Oral pan-RAS(ON) inhibitor; locks multiple active RAS mutants (including G12D, G12V) in a signaling-incompetent state	Cytotoxic regimens (e.g. nal-irinotecan/5-FU, FOLFOX, gemcitabine-based) with no RAS-pathway specificity
Median overall survival	13.2 months (primary analysis); 12.4 months (ad hoc analysis)	6.7 months
Median progression-free survival	7.2 months	3.6 months
Characteristic toxicity	ILD/pneumonitis (2.4%), GI perforation, dermatologic/soft-tissue toxicity, stomatitis, diarrhea	Regimen-dependent: myelosuppression, neuropathy, GI toxicity typical of cytotoxic chemotherapy
Route and burden	Oral, once daily, outpatient	Most regimens are infusional; higher visit burden

RASolute 302 compared daraxonrasib against a mix of four chemotherapy regimens grouped as a single comparator arm, not against any one regimen individually; select among the chemotherapy options above on the same clinical grounds used before this approval existed.

The toxicities that need a plan, not just a mention

Daraxonrasib's warnings and precautions cover interstitial lung disease or pneumonitis, gastrointestinal perforation, dermatologic and soft-tissue toxicity, stomatitis and other oral disorders, diarrhea, and embryo-fetal toxicity. The one most worth building a monitoring habit around is ILD/pneumonitis: reported in 2.4% of patients across the pooled safety population (0.9% grade 3 or higher, one fatal case), with a median time to first onset of 111 days — meaning the relevant window for new dyspnea or cough is months into therapy, not the first cycle. The label's guidance, as reported, is to withhold the drug if ILD is suspected and to reduce the dose or discontinue permanently if no alternative cause is found. Diarrhea, stomatitis and dermatologic toxicity are more common and more manageable day to day, but worth setting expectations for at initiation rather than reacting to after the fact, the same way oncology teams already counsel patients starting other oral targeted agents. None of the sourcing available to us for this story describes a boxed warning on the US label; given the fatal ILD case in trial, that is a detail worth confirming directly against the full prescribing information rather than assuming from this article.

What's actually available, and where

• United States: available now. FDA approved daraxonrasib 26 August 2026; Revolution Medicines has set a reported wholesale acquisition cost around $39,800 for a 30-day supply (roughly $478,000 a year before discounts, rebates or assistance), with a copay program reported to bring out-of-pocket cost toward $0 for eligible commercially insured patients. No Medicare or Medicaid coverage decision was confirmed in the sourcing for this story — treat payer coverage as uncertain rather than assume it mirrors commercial-insurance access.
• European Union: not yet approved. This CHMP positive opinion is a recommendation; the European Commission still has to issue the binding authorisation, typically within about two months, after which pricing and reimbursement are negotiated separately by each member state — a process that can take considerably longer than the authorisation itself.
• First-line use: not yet approved anywhere. FDA separately granted daraxonrasib Breakthrough Therapy designation in September 2026 for first-line combination use, which remains under review and is not the indication covered by this approval or this CHMP opinion.
• Patient selection: neither the US label nor the CHMP opinion, per available reporting, restricts eligibility to a specific RAS variant — unlike the G12C-only sotorasib and adagrasib, daraxonrasib's approved population is defined by disease stage and prior therapy, not genotype, though RASolute 302's own molecular subgroup data is worth reviewing before extrapolating to every RAS variant equally.

Daraxonrasib's regulatory path so far

1. Aug 26, 2026

   FDA approves daraxonrasib

   Approved in the US as monotherapy for previously treated metastatic pancreatic ductal adenocarcinoma, based on RASolute 302.

2. Sep 15, 2026

   FDA grants Breakthrough Therapy designation

   For a separate, first-line combination use, still under review and not yet approved.

3. Oct 15, 2026

   EMA's CHMP issues a positive opinion

   Recommending EU marketing authorisation for the same previously-treated population, under the agency's new phased-review pilot.

4. Ahead

   European Commission decision expected

   Typically within about two months of a positive CHMP opinion; pricing and reimbursement follow separately by member state.

Frequently asked questions

Is Rasonque (daraxonrasib) available in the US right now?

Yes. FDA approved it on 26 August 2026 as monotherapy for adults with metastatic pancreatic ductal adenocarcinoma who have had at least one prior systemic therapy, or who cannot tolerate multiagent chemotherapy. It is already prescribable; Revolution Medicines has set a reported wholesale acquisition cost around $39,800 for a 30-day supply, with a copay program for eligible commercially insured patients. The EU is not yet approved — the European Commission still has to act on this CHMP opinion.

Which patients were studied, and how big was the survival benefit?

RASolute 302, the Phase 3 trial behind both the US approval and the EU opinion, randomized about 500 adults with previously treated metastatic pancreatic ductal adenocarcinoma 1:1 to daraxonrasib 300 mg once daily or investigator's choice of one of four chemotherapy regimens. Median overall survival was 13.2 months on daraxonrasib versus 6.7 months on chemotherapy (hazard ratio 0.40); progression-free survival was 7.2 versus 3.6 months. A later ad hoc analysis reported a closer 12.4-month daraxonrasib figure against the same 6.7-month comparator, which reporting describes as broadly consistent with the primary result.

What should I watch for once a patient starts daraxonrasib?

Interstitial lung disease or pneumonitis, reported in 2.4% of patients (0.9% grade 3 or higher, one fatal case), with a median time to onset of about 111 days — so the risk doesn't front-load into the first weeks of therapy. The label also carries warnings for gastrointestinal perforation, dermatologic and soft-tissue toxicity, stomatitis, diarrhea and embryo-fetal toxicity. None of these were reported as a boxed warning in the sourcing available to us; confirm directly against the full prescribing information before prescribing.