VJToday

FDA approves daraxonrasib for metastatic pancreatic cancer

On August 26, 2026, the U.S. Food and Drug Administration (FDA) granted approval to daraxonrasib, a RAS(ON) multi-selective inhibitor, in patients with pre-treated metastatic pancreatic ductal adenocarcinoma (PDAC).1 Over 90% of PDAC tumors harbor activating RAS pathway alterations, most commonly KRAS mutations, making oncogenic RAS an attractive therapeutic target. However, direct targeting of RAS-driven cancers has historically proven challenging, creating a major unmet need for effective biomarker-directed therapies in metastatic PDAC.2,3

The approval is based on findings from the Phase III RASolute 302 trial (NCT06625320) presented at the 2026 American Society of Clinical Oncology (ASCO) Meeting, evaluated daraxonrasib in patients with previously treated metastatic PDAC. A total of 500 patients were randomized 1:1 to receive either daraxonrasib or a chemotherapy regimen selected at investigator discretion. Overall survival (OS) and progression-free survival (PFS) among patients carrying RAS G12 mutations served as co-primary endpoints, while OS and PFS across the broader patient population, along with objective response rate (ORR) and overall safety, were evaluated as secondary measures.4

The co-primary endpoints were achieved; among RAS G12-mutated patients, median OS reached 13.2 months with daraxonrasib compared to 6.7 months on chemotherapy (HR 0.40, 95% CI: 0.30–0.54). Median PFS followed a similar pattern, at 7.3 months versus 3.5 months (HR 0.45, 95% CI: 0.34–0.59). Safety findings aligned with earlier trial data, with the most common adverse events being gastrointestinal issues, fatigue, and skin rash. Rates of treatment discontinuation stayed comparatively low, notably given the advanced stage of disease in this population. 4

Zev Wainberg, MD, University of California, Los Angeles, CA, who was involved in the pivotal trial, comments on the transformative effect of daraxonrasib in patients, stating:

“The group of patients who received daraxonrasib outperformed the group of patients who received chemotherapy in every aspect, response rate, progression-free survival, more importantly, overall survival, doubling the overall survival from about 6.7 to 13.2. So really a consistent result across the board. It also made those patients feel better because even despite side effects, which are notable, the quality of life improvement scale was significantly better in the group of patients who received eribulin over those who received chemotherapy.”

This approval represents the first biomarker-driven therapy to demonstrate an overall survival advantage in metastatic PDAC, and has the potential to become a new standard of care, which may also pave the way for future RAS-targeted combination strategies in pancreatic cancer.

References:

  1. U.S. Food and Drug Administration. FDA Approves First in Class Targeted Therapy for Metastatic Pancreatic Cancer. Available here. (Last Accessed 26/08/2026).
  2. Nagaraju GP, Nellipudi H, Ganji C, Kuppala V, Ganji SP, Kumari S, et al. Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions. Signal Transduct Target Ther. 2026;11(1).
  3. Alanazi FE, Alatawi Y, Alattar A, Alshaman R, Kotb AA, Hetta HF. Broad-spectrum ras inhibition in pancreatic ductal adenocarcinoma: Mechanistic advances and therapeutic promise. Pharmaceuticals (Basel) 2025 Nov 24;18(12):1788.
  4. Wolpin BM, Wainberg ZA, Hendifar A, 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. J Clin Oncol. 2026;44(suppl 17):Abstr LBA5.