Professor Brian Wolpin

A once-daily oral RAS inhibitor has doubled median overall survival in previously treated metastatic pancreatic cancer, with results hailed as a new standard of care.

The phase 3 RASolute 302 trial found daraxonrasib extended median overall survival to 13.2 months in patients with RAS G12 mutations, compared with 6.6 months for chemotherapy, a 60% reduction in the risk of death (HR 0.40; p<0.001). Results were presented at the 2026 ASCO Annual Meeting, prompting a rare standing ovation, and were concurrently published in the New England Journal of Medicine [link here].

“These results support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said Professor Brian Wolpin of Dana-Farber Cancer Institute and Harvard Medical School, who presented on behalf of the RASolute 302 investigators.

Key results

The 500-patient trial enrolled adults from six countries with confirmed metastatic pancreatic ductal adenocarcinoma, known RAS mutation status and disease progression after one line of therapy. Participants were randomised to daraxonrasib 300 mg once daily or investigator’s choice of chemotherapy. RAS G12 mutations were identified in 91.8% of participants.

Professor Wolpin noted that second-line chemotherapy delivers median PFS of just three to four months and median OS of six to seven months. RAS mutations are present in more than 90% of PDACs, most commonly KRAS G12D, G12V and G12R, and no approved RAS-targeting therapy had previously been available for pancreatic cancer.

Safety

Patients on daraxonrasib remained on treatment for a median of 6.2 months versus 1.5 to 3.2 months across chemotherapy regimens. Dose reductions due to treatment-related adverse events occurred in 36% of daraxonrasib patients, compared with almost 60% on chemotherapy, with treatment discontinuation rates of 1% versus 11% respectively.

The most common adverse events prompting dose reduction with daraxonrasib were rash, diarrhoea and stomatitis. For chemotherapy, they were low blood counts, fatigue, diarrhoea and peripheral neuropathy. Serious treatment-related adverse events leading to hospitalisation were GI events in both arms.

Expert comment

Dr Jennifer Knox of the Princess Margaret Cancer Centre in Toronto said the trial delivered a new standard of care in the second-line setting and called for RAS-targeted therapy to drive future trials across the full spectrum of pancreatic cancer.

“An incredibly important finding is the improvement in the time to deterioration of pain as a symptom, as well as the global quality of life, because these patients are so very sick,” she said.

Dr Rachna Shroff, co-leader of the GI clinical research team at the Arizona Comprehensive Cancer Center, called the findings a “game-changer.”

“The idea of targeting KRAS has always been the holy grail in pancreas cancer, because it is nearly ubiquitous and it is an early driver of pancreas cancer growth and progression,” she said. “The doubling of median survival and a reduced risk of death by 60% have never been seen before in previously treated pancreatic cancer.”

The RASolute 302 study was supported by Revolution Medicines.

A STANDING OVATION for Dr. Brian Wolpin at #ASCO2026 !

The scientific community just rose to its feet to honor a discovery that could change the future of pancreatic cancer care. His leadership in the phase 3 trial of #daraxonrasib has delivered a major survival breakthrough… pic.twitter.com/qvEF96LfOD

— Dr. Iván R. González (@Dr_Ivanoncologo) June 2, 2026