Oral daraxonrasib doubles survival time in pancreatic cancer: New data
Large trial testing drug vs. standard chemo in previously treated patients
Written by |
Treatment with Revolution Medicines‘ oral daraxonrasib more than doubled overall survival versus standard chemotherapy among adults with previously treated metastatic pancreatic cancer in a large, late-stage clinical trial.
That’s one of the key findings of newly published results from the ongoing RASolute 302 Phase 3 clinical trial (NCT06625320), which is testing the therapy candidate in 500 people ages 18 and older with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. Metastatic means the cancer has spread. The new data also show that patients given daraxonrasib survived more than twice as long before their disease worsened.
“In this trial, daraxonrasib redefined treatment expectations in previously treated metastatic pancreatic cancer by reducing the risk of death by 60% and increasing median overall survival to more than one year, a result not previously reported in any Phase 3 clinical trial in any line of therapy for this disease,” Mark A. Goldsmith, MD, PhD, Revolution’s CEO and chairman, said in a company press release summarizing the new data.
“These striking results firmly support daraxonrasib as the new standard of care for patients with previously treated metastatic pancreatic cancer,” Goldsmith said.
Revolution intends to submit these data to the U.S. Food and Drug Administration (FDA) as part of an approval application under a Commissioner’s National Priority Voucher pilot program, which offers an ultra-rapid review process for applications addressing urgent health priorities in the U.S. The FDA last month authorized an expanded access program that allows eligible patients to receive the drug outside a clinical trial while regulatory review is ongoing.
The new trial data were published in the New England Journal of Medicine, in a study titled “Daraxasonib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer.” The findings were also presented during a late-breaking session at the 2026 American Society of Clinical Oncology (ASCO) annual meeting, held recently in Chicago.
More than 90% of PDAC tumors carry mutations in the RAS gene family, which acts like an on/off switch controlling cell growth. When RAS is mutated, it becomes stuck in the on position, driving uncontrolled tumor growth.
Poor survival seen for patients with available treatment
For patients whose cancer has come back or kept growing after their first round of chemo, standard second-line chemotherapy typically offers limited benefit. Survival for these individuals averages about 6-7 months.
Daraxonrasib is an oral medication that belongs to a new class of drugs called RAS(ON) multiselective inhibitors, which are designed to block the active, or on, state of both mutant and wild-type (normal) RAS proteins. The therapy targets a broad range of RAS variants, which is relevant because PDAC tumors carry a variety of RAS mutations.
“Revolution Medicines has been singularly focused on developing bold new targeted medicines for treating patients with RAS-driven cancers, which are some of the most aggressive and difficult-to-treat diseases in oncology,” Goldsmith said.
The FDA has named daraxonrasib a breakthrough therapy and granted it orphan drug status as a second-line treatment for people with metastatic PDAC with G12 mutations in the RAS gene — the most common type of RAS mutation in PDAC. These regulatory designations are intended to speed the development and review of new drug candidates for rare conditions that outperform available therapies.
RASolute 302 enrolled adults with previously treated metastatic PDAC across 59 sites in six countries. Participants were randomly assigned to receive either once daily daraxonrasib (300 mg) or the investigator’s choice of one of four standard chemotherapy regimens. Nearly all patients (92%) had RAS G12 mutations.
The trial’s main goals were to measure overall survival and progression-free survival, or how long a patient lived without disease progression. These were measured specifically in patients with RAS G12 mutations and also in the full group. Data were collected through Feb. 10 of this year, with an average follow-up time of 8.5 months.
Daraxonrasib extended overall survival to a median of 13 months
Among those with RAS G12 mutations, treatment with daraxonrasib doubled the median overall survival compared with chemotherapy (13.2 vs. 6.6 months). This translated to a 60% lower risk of death. Similar results were observed across the entire group of participants (13.2 vs. 6.7 months).
Patients on daraxonrasib survived more than twice as long before their disease worsened — 7.3 months versus 3.5 months in the RAS G12 group — representing a 55% lower risk of progression, the data showed. Results were similar across the full patient group (7.2 vs. 3.6 months).
Three times as many patients with G12 mutations taking daraxonrasib saw their tumors meaningfully shrink compared with those on chemotherapy — about 1 in 3 versus approximately 1 in 9. Similar results were seen across all patients (32% vs. 11%).
Patients taking daraxonrasib also reported feeling better for longer. These individuals experienced a meaningful delay before their pain worsened — 9.2 months compared with 3.8 months for chemotherapy patients. Their overall health status and quality of life also held up longer: 5.7 months versus 2.6 months before a meaningful decline.
These results will change how scientists, clinicians, and patients think about treatment for pancreatic cancer, and support a new paradigm where RAS(ON) inhibition enters standard of care for patients with previously treated metastatic pancreatic adenocarcinoma.
In terms of safety, treatment-related adverse events (TRAEs) of grade 3 or higher (severe) occurred in fewer daraxonrasib-treated patients than in those receiving chemotherapy (44% vs. 58%). The most common severe TRAEs associated with daraxonrasib were rash, affecting 14%, and stomatitis or mouth sores, experienced by 12%. Very few patients stopped treatment because of side effects due to daraxonrasib compared with chemotherapy (1% vs. 11%).
Brian M. Wolpin, MD,  the trial’s principal investigator, from the Dana-Farber Cancer Institute in Boston, noted that “for many patients, second line chemotherapy provides modest benefits.” As such, “new treatments delivering more durable tumor control have been urgently needed,” Wolpin said
“In this global randomized trial, daraxonrasib, an oral RAS(ON) inhibitor, doubled median overall survival compared to standard of care chemotherapy for patients with previously treated metastatic pancreatic cancer,” Wolpin said. “These results will change how scientists, clinicians, and patients think about treatment for pancreatic cancer, and support a new paradigm where RAS(ON) inhibition enters standard of care for patients with previously treated metastatic pancreatic adenocarcinoma.”
