The phase 3 RASolute 302 trial (NCT06625320) evaluating daraxonrasib has demonstrated a significant improvement in overall survival (OS) for patients with pretreated metastatic pancreatic ductal adenocarcinoma (PDAC), according to Diane Simeone, MD. The findings represent a notable advancement for a patient population that has historically faced limited therapeutic options after progression on standard chemotherapy.
In the trial, daraxonrasib, a novel oral anti-RAS(ON) therapeutic, was administered once daily and compared with standard-of-care chemotherapy. The study focused on the second-line setting, specifically enrolling patients who had previously received systemic treatment. Simeone noted that the results were clinically significant, as the investigation showed that daraxonrasib approximately doubled the median OS compared with the control arm. Specifically, the median OS was 13.2 months for those receiving the RAS inhibitor vs 6.7 months for those on standard chemotherapy.
This survival benefit is particularly relevant given that approximately half of all patients with pancreatic cancer present with metastatic disease at the time of diagnosis. While advancements in early detection strategies are ongoing, Simeone highlighted the immediate impact of this therapeutic for patients currently seen in clinical practice. By utilizing innovative chemistry to target KRAS, a protein previously considered undruggable, this regimen offers a meaningful opportunity to extend the life of patients with metastatic PDAC.
Simeone is the director of the Moores Cancer Center at UC San Diego Health.
Transcript:
Clearly, with some smart chemistry and determination, there have been a number of new approaches to make novel KRAS-targeting drugs. With the new agent, daraxonrasib—that was produced by Revolution Medicines—they have now shown the results of their phase 3 RASolute 302 clinical trial that was used to evaluate this agent in the second-line setting. By that, I mean patients who already had been treated with standard chemotherapy. Here, they were either given the anti-RAS therapeutic, which was an oral agent, once a day, comparing that to whatever they were on standard-of-care chemotherapy. There, the results were quite significant in that it [approximately] doubled the [median] overall survival in the second-line setting, which was [13.2] months vs 6.7 months. That’s a huge benefit for patients. Of course, these are patients with metastatic pancreas cancer, patients who already have tumors that have spread to multiple organs. Unfortunately, those have been tough patients to treat, and that’s about half of [patients with] pancreatic cancer who come in the door when they present. We still haven’t had effective early detection strategies for pancreas cancer, although we’re starting to really move the needle in that space—that’s a separate thing to talk about. Certainly, for patients we’re seeing in the clinic every single day, this is impactful in improving their length of life and hopefully their quality of life.
Reference
Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines Inc. April 13, 2026. Accessed April 21, 2026. https://tinyurl.com/44t5vh5d
