Daraxonrasib, second-line pancreatic cancer treatment, 'truly remarkable' | 2026 ASCO

Shubham Pant, M.D., M.B.B.S., says there has been little to celebrate in the second-line treatment of pancreatic cancer in decades.

“Having done pancreatic cancer for about two decades now, we've had only one positive second-line trial, which was 5FU liposomal irinotecan in the second-line setting versus 5FU, and we've had a host of, maybe 20-plus, negative trials in the second-line setting,” said Pant, a professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center in Houston, in an interview with Managed Healthcare Executive.

Pant and other oncologists, especially those who take care of pancreatic cancer patients, said results reported today for daraxonrasib at the 2026 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago are a major exception to what has been the dismal rule for second-line treatment of pancreatic cancer. The findings from an open-label, phase 3 trial that are scheduled to be presented at the meeting’s plenary session this afternoon show that the overall survival of the 228 patients randomly selected to be treated with daraxonrasib was more than twice as long (13.2 months vs. 6.7 months) as 231 who were treated with the investigator’s choice of chemotherapy. Results for progression-free survival suggest a sizable treatment effect from daraxonrasib (7.2 months for the daraxonrasib group versus 3.6 months for the chemotherapy group). The primary end point of the trial was overall survival and progression-free survival in patients with the RAS gene mutation that is most common among pancreatic cancer patients.

Pant, who was one of the investigators on the trial called RASolute 302, said any positive trial is remarkable in pancreatic cancer. “Completely changing — transforming — the care of these patients is truly remarkable,” he said of daraxonrasib.

The news about daraxonrasib was not unexpected, despite the RASolute 302 findings having the coveted status of a presentation at a plenary session. Positive results from the phase 1 trial of daraxonrasib were reported in the New England Journal of Medicine earlier this month. The New York Times and other media outlets have published articles about the drug.

The clinical trials assessing daraxonrasib were supported by the drug’s developer, Revolution Medicines, a biotech company headquartered in Redwood City, California.

Daraxonrasib targets a protein that Pant compared to a shiny ball that drugs slip off of. But it is equipped with a “molecular glue” that sticks to proteins generated by mutated versions of the RAS gene. Pant described daraxonrasib as a “pan-RAS inhibitor” because it appears to be effective against pancreatic cancer associated with a variety of RAS mutations, not just the most common one, RAS G12.

The ASCO abstract says that 43.6% of the patients in the daraxonrasib group had serious side effects (grade 3 or greater treatment-related adverse events) compared with 57.5% who were treated with the investigator’s choice of chemotherapy. that 90% of the patients treated with daraxonrasib experience a rash that can be managed fairly easily with antibiotic skin creams and protection from the sun. He said about 15% get a more serious rash that may require stopping treatment but that patients usually recover quickly and resume treatment.