Researchers report that daraxonrasib, an oral drug designed to block RAS-driven cancer signals, has shown encouraging results in an early clinical trial for advanced pancreatic cancer, producing notable disease control and manageable side effects while remaining investigational pending larger trials.
Daraxonrasib is a daily pill meant to shut down multiple cancer signals tied to the RAS pathway, a mutation present in over 90% of pancreatic tumors. The drug just completed its first-in-human phase 1/2 study led by investigators at Dana-Farber and published in The New England Journal of Medicine, testing safety and early signs of benefit. All 168 trial participants had advanced disease and had previously received at least one chemotherapy regimen.
Unlike older agents that only hit rare RAS variants, daraxonrasib was developed to act against multiple active RAS signals, aiming to cover the mutations most commonly found in pancreatic tumors. At the planned 300-milligram dose, roughly 30% of patients experienced a measurable tumor response. Across the cohort, about 90% of patients had their cancer either shrink or stop progressing at some point on the drug.
Side effects were frequent but generally manageable, with rash, mouth inflammation, nausea and diarrhea reported most often. Investigators said most patients tolerated treatment with supportive care and few stopped therapy because of toxicity. Because this was an early-phase study, the safety profile will continue to be monitored closely in larger trials.
“If supported by data from future clinical trials, daraxonrasib would be a targeted therapy relevant to nearly all patients with advanced pancreatic cancer,” he said. “This trial provides the first published data showing the safety and broad activity of a RAS(ON) multi-selective inhibitor in pancreatic cancer,” Wolpin went on. “If it proves effective in larger clinical trials, it would signify a substantial shift in how this disease is treated.”
Investigators cautioned that the phase 1/2 design did not include a randomized control arm comparing daraxonrasib directly to chemotherapy, so the results cannot definitively prove superiority. “The study did not include a randomized control arm that directly compared daraxonrasib with chemotherapy,” he said. “That being said, the results for daraxonrasib looked substantially better than what we have seen in prior clinical trials of chemotherapy in patients with previously treated metastatic pancreatic cancer.”
The team acknowledged remaining unknowns, including how the drug might perform earlier in the disease course or how best to combine it with other therapies. For patients and families facing pancreatic cancer, the lead investigator described the findings as signaling “real momentum” toward more effective options, while stressing the agent remains investigational and is not a cure. “Pancreatic cancer remains a challenging disease, and additional research is needed to determine how best to sequence or combine therapies to provide the most durable responses and cures,” he said.
Outside experts reacted with cautious optimism, noting the potential impact if larger datasets confirm the early signals. “We are anxiously awaiting the upcoming plenary presentation of RASolute 302 at the ASCO meeting later this month,” said one commentator. “Greater than 90% of pancreatic cancers have activation of kRAS, which is a major factor in the development and progression of these cancers.”
“If the full dataset results that will be reported later this month confirm what was earlier released, I believe this will be one of the most important breakthroughs in all solid tumors,” Slomovitz went on. “Doubling the survival time in pretreated patients is unprecedented.” He added a note of realism about the need to review the full efficacy and safety data before changing practice: “We will need to evaluate the full dataset for efficacy and safety,” Slomovitz added. “I am more than cautiously optimistic, and I am truly excited for our patients and their families that suffer from this dreadful disease.”
