Daraxonrasib roughly doubles survival over chemotherapy in previously treated metastatic pancreatic cancer

In the Phase 3 RASolute 302 trial, the investigational oral RAS inhibitor from Revolution Medicines cut the risk of death by 60 percent versus investigator's-choice chemotherapy.

Metastatic pancreatic cancer that has already progressed on one line of treatment is among the bleakest settings in oncology: second-line chemotherapy typically extends median survival by only a few months. A peer-reviewed Phase 3 trial published in the New England Journal of Medicine now reports that daraxonrasib (RMC-6236), an investigational oral RAS inhibitor from Revolution Medicines, roughly doubled median overall survival against chemotherapy in this population.

In RASolute 302, an international, open-label, randomized trial, 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC) were assigned to daraxonrasib (248 patients) or chemotherapy of the investigator’s choice (252 patients). Of those enrolled, 91.8 percent carried RAS G12 mutations. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor that targets the active, GTP-bound state of both mutant and wild-type RAS — the pathway aberrantly activated in more than 90 percent of pancreatic ductal adenocarcinoma cases.

What the trial measured

The trial had dual primary endpoints: overall survival (OS) and progression-free survival (PFS), both assessed in the subpopulation of patients with G12 mutations. In that G12 population, median overall survival was 13.2 months with daraxonrasib versus 6.6 months with chemotherapy, a hazard ratio of 0.40 (P<0.001). In the overall population — which also included patients with G13 or Q61 mutations or no identified mutation — median OS was 13.2 months versus 6.7 months, again a hazard ratio of 0.40 (P<0.001), corresponding to a 60 percent reduction in the risk of death.

Median overall survival was 13.2 months with daraxonrasib versus 6.6 months with chemotherapy in the G12 population, a hazard ratio of 0.40.

Progression-free survival moved in the same direction. In the G12 population, median PFS was 7.3 months with daraxonrasib versus 3.5 months with chemotherapy (hazard ratio 0.45); in the overall population it was 7.2 versus 3.6 months (hazard ratio 0.49), with P<0.001 for both comparisons. Objective response and patient-reported quality of life were among the key secondary endpoints, alongside OS and PFS in the overall population.

On tolerability, treatment-emergent adverse events were reported in all daraxonrasib-treated patients and in 97.7 percent of chemotherapy patients. Grade 3 or higher adverse events were actually less frequent with daraxonrasib (61.8 percent) than with chemotherapy (69.6 percent). Treatment-related adverse events leading to discontinuation occurred in 1.2 percent of the daraxonrasib group versus 11.2 percent of the chemotherapy group.

A few caveats temper the numbers. Crucially for patients, daraxonrasib is investigational: it is not approved by the FDA or any other regulator for previously treated metastatic pancreatic cancer, or any indication, and is therefore not a currently available treatment. On May 1, 2026, the FDA authorized an expanded-access protocol allowing eligible U.S. patients with previously treated mPDAC to obtain the drug through their physicians while it remains under review, but expanded access is not the same as approval. The trial was also open-label, so patients and investigators knew which treatment was given — a design that can introduce bias, though OS is a relatively objective endpoint. The study was funded by Revolution Medicines, and several authors are company employees. Per the ClinicalTrials.gov registry (NCT06625320), the primary completion date was June 2026, so these are the pivotal readout data rather than a final, fully mature dataset; results had not been posted to the registry at the time of publication. The trial enrolled patients with documented RAS status who had received one prior line of 5-fluorouracil-based or gemcitabine-based therapy.

The authors conclude that, among patients with previously treated mPDAC, daraxonrasib led to significantly longer overall and progression-free survival than chemotherapy. This is a peer-reviewed report, not a preprint, and reflects human clinical data rather than preclinical findings. This article is journalism and not medical or investment advice.

Trials Today

Phase 3 VECTRA-01 (AZD2265 / 225Ac-PSMA-I&T, mCRPC) — Recruiting; alpha-emitter PSMA radioligand vs SOC after prior beta-emitter, taxane and ARPI; ~670 patients; dual primary rPFS and OS.

Phase 3 PRECISE-HD (pridopidine, Huntington's disease) — Newly registered; 400 patients not on antidopaminergics; primary is 52-week change in composite cUHDRS.

Phase 3 QUILT-2.023 (nogapendekin alfa inbakicept, 1L NSCLC) — Terminated; sponsor registry note states no active subjects, no efficacy results posted (enrolled 102).

Phase 3 Atezolizumab + standard HER2 therapy, 1L HER2+ mBC (NRG/NCI) — Terminated for poor accrual (190 enrolled); posted PFS 52.3% vs 40.5% is a numerical, underpowered signal only (CIs overlap, no HR).

Phase 2/3 Peri-operative nivolumab + ipilimumab, esophageal/GEJ adenocarcinoma (NCI) — Suspended after enrolling 278; registry summary gives no reason, so cause is unconfirmed. Watch item.

At the Agencies

Baxdrostat (Baxfendy), AstraZeneca — FDA approval May 18, 2026; first-in-class aldosterone synthase inhibitor for uncontrolled/resistant hypertension; BaxHTN placebo-adjusted SBP -9.8 mmHg.

Bulevirtide (Hepcludex), Gilead — FDA accelerated approval May 22, 2026; first US therapy for chronic hepatitis delta; surrogate week-48 combined response 48% vs 2%, confirmatory data required.

Pivekimab sunirine (Decnupaz), AbbVie — FDA approval May 27, 2026; first CD123-directed ADC for ultra-rare BPDCN; single-arm CADENZA CR/CRc 69.7% in treatment-naive (n=33).

Nerandomilast (Jascayd), Boehringer Ingelheim — EMA CHMP — Positive CHMP opinion (18-21 May 2026) for IPF and PPF; oral PDE4B inhibitor; FIBRONEER-IPF met primary FVC endpoint, key secondary not met. EC decision pending.