Dr Pant on the Potential Significance of Daraxonrasib for PDAC Management

Having treated patients with pancreatic cancer for over 20 years, these are truly remarkable findings [for daraxonrasib].

Shubham Pant, MD, MBBS, a professor in the Departments of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics, as well as director of Clinical Research at The Sheikh Zayed Center For Pancreatic Cancer Research at The University of Texas MD Anderson Cancer Center, discussed findings from the phase 3 RASolute 302 trial (NCT06625320) evaluating the RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236) in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). He also highlighted what this agent may mean for the pancreatic cancer field.

Data from RASolute 302 presented at the 2026 ASCO Annual Meeting showed that in the population of patients with RAS G12–mutant disease, daraxonrasib (n = 228) generated a median overall survival (OS) of 13.2 months (95% CI, 10.0-not estimable [NE]) compared with 6.6 months (95% CI, 5.4-8.2) for investigator’s choice of chemotherapy (n = 231; HR, 0.40; 95% CI, 0.30-0.54; P = 5.9×10⁻¹⁰). In the overall trial population, the median OS was 13.2 months (95% CI, 10.0-NE) for daraxonrasib (n = 248) vs 6.7 months (95% CI, 5.8-8.0) for chemotherapy (n = 252; HR, 0.40; 95% CI, 0.30-0.53; P = 4.6 × 10^–11).

On July 23, 2026, the FDA accepted for review a new drug application seeking the approval of daraxonrasib for the treatment of patients with previously treated metastatic PDAC, based on the RASolute 302 findings.

Daraxonrasib acts like a molecular glue, Pant said, describing the RAS pathway as a light switch that becomes stuck in the “on” position and continually signals the cancer cell to grow; the agent binds that switch and turns it off, driving the cancer cell to die. Because approximately 90% of pancreatic cancers are driven by KRAS mutations, the trial is highly relevant to the disease, he added.

The magnitude of the OS benefit stood out to Pant, who noted that most trials in pancreatic cancer have been negative and that even positive studies have typically delivered gains measured in weeks to a couple of months. A near doubling of survival with daraxonrasib is remarkable in this setting, he said.

If approved, daraxonrasib would offer a much-needed new option for a patient population that has historically seen few meaningful advances, Pant concluded.