RASolute 302 Brings a “Transformative” Moment in Pancreatic Cancer: A 60% Improvement in Overall Survival

Two nights before the data were announced, “transformative” was the word used to describe the results for RASolute 302 (NCT06625320), the phase 3 trial that was the talk of the 2026 meeting at the American Society of Clinical Oncology (ASCO).

The landmark study testing the RAS(ON) inhibitor daraxonrasib in pancreatic ductal adenocarcinoma (PDAC) delivers: results presented in the plenary session showed that overall survival (OS) improved 60%, more than doubling the rate of patients receiving chemotherapy.¹

As Revolution Medicines CEO Mark A. Goldsmith, MD, PhD, fielded questions May 29, 2026, at a STAT News forum, he predicted that these results would be the start of pancreatic cancer moving from one of the most intractable medical challenges to a chronic condition. Although the study presented May 31, 2026, involved patients in the second-line setting, speculation is ablaze when patients can get daraxonrasib at diagnosis—and these studies are under way.

“Few therapies are available for patients with previously treated metastatic pancreatic cancer, and these therapies have modest efficacy and substantial toxicities,” lead investigator Brian Wolpin, MD, MPH, Hale Family Center for Pancreatic Cancer Research and Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts, said in ASCO’s statement. “The RASolute 302 trial was designed to assess a RAS(ON) multi-selective inhibitor as a second-line treatment for patients with metastatic pancreatic cancer, looking to define a new standard of care for these patients that works better and has less side effects than currently available chemotherapies.”

Results were simultaneously reported in the New England Journal of Medicine.²

One of Medicine’s Greatest Challenges

PDAC is lethal, stubborn, and increasingly common. According to the American Cancer Society, in 2026, roughly 67,500 Americans will receive the diagnosis, and more than half will already have metastatic disease at the time they are told. For those patients, the 5-year survival rate is stuck at around 3%. When first-line chemotherapy stops working—and it almost always does—second-line treatment has offered only modest relief—a median progression-free survival (PFS) of 3 to 4 months and a median OS of perhaps 6 to 7 months, Wolpin stated in his plenary presentation, which drew a standing ovation as the Thanksgiving pie-sized gap of the Kaplan-Meier curves filled the screens in the lecture hall.

More than 90% of pancreatic cancers are driven by mutations in the KRAS gene, most commonly at codon G12. KRAS produces a protein that normally acts as a molecular on/off switch for cell growth; when mutated, the switch gets stuck in the "on" position, fueling uncontrolled tumor proliferation. For years, this oncogene was considered "undruggable." Even as KRAS-specific inhibitors emerged in lung cancer, pancreatic cancer remained resistant to such targeted approaches—in part because its mutations are more varied, and in part because RAS signaling drives tumor growth even in the minority of cases without an identifiable RAS mutation.

A New Kind of Inhibitor

Daraxonrasib from Revolution Medicines represents a fundamentally different approach. Rather than targeting a single mutant form of RAS, it is a RAS(ON) multi-selective, tri-complex inhibitor that binds and blocks the active, GTP-bound state of both wild-type and mutant RAS, including the G12, G13, and Q61 variants most commonly found in pancreatic cancer. Crucially, it comes as a once-daily oral pill, a departure from intravenous chemotherapy regimens.

The Trial Design and the Study Population

The RASolute 302 was a global, randomized, open-label phase 3 trial enrolling 500 patients across 59 sites in North America, Europe, and Asia. Participants had metastatic PDAC and had received 1 prior line of chemotherapy. They were randomly assigned 1:1 to receive either daraxonrasib (300 mg daily) or the investigator's choice among 4 standard-of-care chemotherapy regimens. The dual primary endpoints were OS and PFS in patients harboring a RAS G12 mutation; meaning, a population representing the vast majority of participants (228 in the daraxonrasib arm, 231 in the chemotherapy arm).

All patients were eligible regardless of RAS mutation status, a choice that reflected the drug's broad mechanism of action.

Unprecedented Results Have Gained Attention

At a median follow-up of 8.5 months, daraxonrasib met every primary and key secondary endpoint, and the magnitude of the benefit was striking by any standard in this disease. ASCO gastroenterology expert Rachna Shroff, MD, MS, FASCO, chief of hematology/oncology at the University of Arizona Cancer Center, called results were "landscape-changing” and said when she received the press release, “I started crying in the clinic.”

Median OS reached 13.2 months in the daraxonrasib group, compared with 6.6 months in the chemotherapy group among patients with a RAS G12 mutation—a hazard ratio of 0.40, meaning a 60% reduction in the risk of death. Results were nearly identical in the overall population: 13.2 months versus 6.7 months, with the same hazard ratio of 0.40. This is, in practical terms, nearly a doubling of survival.

PFS told a similar story. Patients on daraxonrasib had a median PFS of 7.3 months (RAS G12) and 7.2 months (overall), compared with 3.5 and 3.6 months on chemotherapy, respectively—representing a more than doubling of time before disease progression.

The objective response rate, which is the proportion of patients whose tumors shrank meaningfully, was 33.2% with daraxonrasib versus 11.8% with chemotherapy in the RAS G12 population, a nearly 3-fold increase. Tumor shrinkage, in turn, translated into real clinical benefit: patient-reported outcomes showed statistically significant delays in pain worsening and deterioration of global quality of life for those receiving daraxonrasib.

A Drug Better Tolerated Than Chemotherapy

Serious side effects were also notably lower. Grade 3 or higher treatment-related adverse events occurred in 43.6% of daraxonrasib patients versus 57.5% in the chemotherapy group. Perhaps most telling: only 1.2% of patients on daraxonrasib discontinued treatment due to side effects, compared with 11.2% on chemotherapy. The most common daraxonrasib-related toxicities were rash and stomatitis—in contrast to chemotherapy's toll of neutropenia, anemia, fatigue, and neuropathy.

Shroff described the study as "a proof of principle that targeting the RAS signaling pathway is critical in the treatment of pancreatic cancer." Revolution Medicines has announced plans to submit the RASolute 302 data to the FDA to support approval of daraxonrasib as a new standard of care for second-line metastatic PDAC.

References

1. Wolpin BM, Wainberg ZA, Hendifar A, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):Abstr LBA5.
2. O’Reilly EM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. Published online May 31, 2026. DOI: 10.1056/NEJMoa2605555