FDA Approves Daraxonrasib for Metastatic Pancreatic Ductal Adenocarcinoma

The FDA has approved daraxonrasib (Rasonque) for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or are not candidates for multi-agent systemic therapy.¹

Daraxonrasib is an oral RAS(ON) multiselective inhibitor. The approval was supported by findings from the phase 3 RASolute 302 trial (NCT06625320), which were presented at the 2026 ASCO Annual Meeting (ASCO 2026). In the trial, daraxonrasib produced a median overall survival (OS) of 13.2 months vs 6.7 months with investigator’s choice of chemotherapy in the overall population.

How was the RASolute 302 trial designed?

RASolute 302 was a global, randomized trial that evaluated daraxonrasib vs investigator’s choice of chemotherapy in adult patients with metastatic PDAC who had received 1 prior fluoropyrimidine- or gemcitabine-based regimen in the metastatic setting and had an ECOG performance status of 0 or 1.² Patients were randomly assigned 1:1 to receive daraxonrasib at 300 mg orally once daily (n = 248) or 1 of 4 investigator’s choice chemotherapy regimens (n = 252). Randomization was stratified by ECOG performance status, metastatic disease status at diagnosis, liver metastasis status at baseline, and tumor RAS mutational status.

The dual primary end points were OS and progression-free survival (PFS) by blinded independent central review (BICR) in the RAS G12–mutated population. Key secondary end points included OS and PFS in the overall population, objective response rate (ORR), and time to deterioration in patient-reported outcomes. The trial enrolled patients at 59 sites across 6 countries; the reported results were based on the first interim OS analysis, at a data cutoff of February 10, 2026, with a median follow-up of 8.5 months (range, 3.2-15.9).

What additional efficacy data were observed in RASolute 302?

Findings reported at ASCO 2026 showed that in the RAS G12–mutated population (daraxonrasib, n = 228; chemotherapy, n = 231), the median OS was 13.2 months (95% CI, 10.0-not estimable [NE]) with daraxonrasib vs 6.6 months (95% CI, 5.4-8.2) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.54; P = 5.9×10⁻¹⁰); the 12-month OS rates were 53.3% vs 18.7%, respectively. In the overall population, the median OS values were 13.2 months (95% CI, 10.0-NE) vs 6.7 months (95% CI, 5.8-8.0), respectively (HR, 0.40; 95% CI, 0.30-0.53; P = 4.6×10⁻¹¹).

The median PFS by BICR in the RAS G12–mutated population was 7.3 months (95% CI, 6.3-8.1) vs 3.5 months (95% CI, 2.9-3.8), respectively (HR, 0.45; 95% CI, 0.34-0.59; P = 3.2×10⁻⁹). In the overall population, these respective values were 7.2 months (95% CI, 5.7-7.5) vs 3.6 months (95% CI, 2.9-4.2; HR, 0.49; 95% CI, 0.38-0.64; P = 5.2×10⁻⁸). The confirmed ORRs by BICR were 33.2% with daraxonrasib vs 11.8% with chemotherapy in the RAS G12–mutated population and 31.6% vs 11.2% in the overall population (P < .0001 for both).

Daraxonrasib also delayed median time to deterioration vs chemotherapy in the symptom of pain (9.2 months vs 3.8 months; HR, 0.51; 95% CI, 0.37-0.71; P < .0001) and median time to deterioration of global health status/quality of life (5.7 months vs 2.6 months; HR, 0.60; 95% CI, 0.46-0.79; P = .0002) in the overall population.

What was the safety profile of daraxonrasib?

Among the 241 patients treated with daraxonrasib in the safety population, grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 43.6% of patients, compared with 57.5% of the 214 patients treated with chemotherapy. Serious TRAEs occurred in 10.8% vs 18.7% of patients, respectively, and 1 grade 5 TRAE (treatment-related pneumonitis) occurred in the daraxonrasib arm. TRAEs led to treatment discontinuation in 1.2% of patients treated with daraxonrasib vs 11.2% of those given chemotherapy.

The most common any-grade TRAEs occurring in more than 15% of patients treated with daraxonrasib were rash (85%), diarrhea (58%), stomatitis (53%), nausea (46%), vomiting (37%), fatigue (23%), anemia (18%), decreased appetite (17%), and paronychia (17%).

References

1. FDA approves first in class targeted therapy for metastatic pancreatic cancer. FDA. August 26, 2026. Accessed August 26, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer?utm_medium=email&utm_source=govdelivery
2. Wolpin BM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. Presented at: 2026 ASCO Annual Meeting; May 29-June 2,2026; Chicago, IL.