For the first time, patients with one of the most aggressive forms of cancer have access to a drug that directly targets the genetic driver of their disease. The U.S. Food and Drug Administration has authorized expanded access to daraxonrasib, an investigational therapy that blocks the mutated KRAS protein responsible for driving more than 90 percent of pancreatic cancers. The decision means more patients can receive the oral drug while it continues to be studied in clinical trials.
Pancreatic cancer has long been considered one of the hardest cancers to treat. KRAS mutations, discovered decades ago, were once dismissed as “undruggable” because their smooth, spherical shape made it nearly impossible for existing medicines to latch on. Daraxonrasib, a first-in-class RAS(ON) tri-complex inhibitor developed by Revolution Medicines, changes that. It works by locking the mutated protein in an inactive state, essentially turning a broken traffic light from green to red. “KRAS mutations in pancreatic cancer are like a traffic light stuck on green that keeps signaling cancer cells to divide and multiply,” said gastrointestinal medical oncologist Dr. Wungki Park of Memorial Sloan Kettering Cancer Center. “Daraxonrasib essentially locks that signal so it can’t get through, causing the cancer cells to slow down or stop growing.”
Results from a phase 1/2 clinical trial published in The New England Journal of Medicine in May 2026 showed that for most patients, the cancer did not worsen for a median of 8.5 months. That is significantly longer than what is typically expected with standard chemotherapy for patients whose disease has already spread and who have received one prior treatment. The trial enrolled 168 patients with stage 4 pancreatic cancer, ranging in age from 30 to 86. All had previously received one line of chemotherapy that had stopped working. Some patients reported symptom improvement within days of starting daraxonrasib, a response rarely seen with conventional chemotherapy. Side effects, including rash, nausea, diarrhea, and mouth sores, affected about one in three patients but were generally manageable. No patients discontinued treatment at the 300-milligram daily dose due to side effects.
Dr. Park said the clinical trial is likely to “open a new paradigm” in treating a disease that is becoming the second leading cause of cancer deaths in the United States. He noted that daraxonrasib appears to work against several common types of KRAS mutations, including G12D, G12V, G12R, and Q61X, which could allow the drug to help a broader group of patients. The FDA previously granted Breakthrough Therapy designation in June 2025 and later accelerated the drug’s review process through a special pilot program.
Phase 3 trials are now underway. Dr. Park is leading a study for patients with metastatic pancreatic cancer who have not yet received any treatment, while Dr. Eileen M. O’Reilly is leading a trial for those who no longer respond to one line of chemotherapy. These studies aim to determine whether daraxonrasib improves overall survival and delays disease progression compared to standard chemotherapy. “Our patients and the pancreatic cancer community are thrilled that we finally have a new drug that may significantly extend the time they have to spend with their loved ones,” Dr. Park said. “I feel like I am finally giving my patients the time they deserve with their loved ones.”