When Brian Wolpin, Professor of Medicine at Harvard Medical School and Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, advanced to the next slide during the plenary session at the 2026 ASCO (American Society of Clinical Oncology) Annual Meeting in Chicago, May 29 to June 2, 2026, the audience of oncology professionals fell silent. The slide showed a Kaplan-Meier survival curve, and what it revealed prompted something rarely seen in a medical conference hall: a 42-second standing ovation, complete with cheering and whistling. The drug at the centre of that moment was daraxonrasib, a novel oral RAS(ON) multi-selective inhibitor developed by Revolution Medicines, and the data it had produced in the Phase 3 RASolute 302 trial were, by any measure, extraordinary.
For patients with metastatic pancreatic ductal adenocarcinoma (PDAC), daraxonrasib had nearly doubled overall survival compared with standard chemotherapy. In one of the most treatment-resistant cancers in existence, that result was not merely clinically significant. It was historic.
Why Pancreatic Cancer Has Resisted Progress for So Long
Pancreatic cancer remains one of the most lethal malignancies in oncology. Roughly 67,500 Americans will receive a diagnosis in 2026 alone, and more than half will already have metastatic disease at the point of diagnosis. For those patients, the five-year survival rate is approximately 3%. When first-line chemotherapy stops working, as it almost invariably does, second-line treatment has historically offered only modest benefit: a median progression-free survival of three to four months and a median overall survival of six to seven months.
The reason for this therapeutic stalemate lies largely in genetics. More than 90% of pancreatic tumours are driven by mutations in the KRAS gene, which encodes a protein that functions as a molecular switch controlling cell growth. In most pancreatic cancers, mutations at positions G12, G13, or Q61 of the KRAS gene lock this switch permanently in the active position, driving uncontrolled tumour proliferation. For decades, scientists considered the RAS protein to be undruggable, its surface too smooth to offer conventional binding sites for small molecules.
The arrival of selective KRAS inhibitors, beginning with sotorasib in KRAS G12C-mutant lung cancer, demonstrated that this barrier was not absolute. But the mutations most common in pancreatic cancer, particularly G12D and G12V, remained without effective targeted agents until daraxonrasib emerged from Revolution Medicines as a first-in-class RAS(ON) multi-selective inhibitor capable of targeting a broad spectrum of RAS variants simultaneously.
The RASolute 302 Trial: Design and Patient Population
The RASolute 302 trial enrolled 500 patients with previously treated metastatic PDAC across global sites. Participants were randomised to receive either once-daily oral daraxonrasib at 300 mg (248 patients) or investigator’s choice of one of four standard cytotoxic chemotherapy regimens (252 patients). The trial was notable for its broad eligibility: it enrolled patients with RAS G12 mutations, including G12D and G12V, as well as those with other RAS variants and patients without an identified tumour RAS mutation, making it the first Phase 3 study to evaluate a RAS(ON) inhibitor across this full spectrum of PDAC.
The primary endpoints were progression-free survival and overall survival. Results were presented during the late-breaking plenary session (Abstract LBA5) on 31 May 2026 and published simultaneously in the New England Journal of Medicine.
Daraxonrasib Results: The Numbers Behind the Standing Ovation
The data were unequivocal. In the RAS G12 population, the primary population of interest, daraxonrasib delivered a median overall survival of 13.2 months compared with 6.6 months for chemotherapy, representing a hazard ratio of 0.40 (95% CI: 0.30–0.54; p<0.0001). This corresponds to a 60% reduction in the risk of death. At 12 months, 53.3% of patients on daraxonrasib were alive, compared with 18.7% on chemotherapy.
The findings in the overall intent-to-treat population were consistent, with a median overall survival of 13.2 months for daraxonrasib versus 6.7 months for chemotherapy, hazard ratio 0.40 (p<0.0001).
Progression-free survival results were equally striking. In the RAS G12 population, median PFS was 7.3 months with daraxonrasib compared with 3.5 months on chemotherapy, a hazard ratio of 0.45 (p<0.0001), representing more than a doubling of the time before disease progression. In the overall population, median PFS was 7.2 months versus 3.6 months.
“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 fewer side effects than currently available chemotherapies,” said Dr Wolpin following the announcement of the topline results in April 2026.
“These results are landscape-changing for metastatic pancreatic cancer patients with a KRAS mutation,” said Rachna Shroff, MD, MS, Chief of the Division of Hematology/Oncology at the University of Arizona Cancer Center and an ASCO Expert in gastrointestinal cancers. “We are seeing unprecedented survival and efficacy in second-line treatment with an expected safety profile. The RAS revolution is here, and this study is proof of principle that targeting KRAS in pancreatic cancer is feasible and effective.”
Julie Gralow, MD, Chief Medical Officer and Executive Vice President of ASCO, described the results at a press conference as not merely a home run but “a grand slam” for both patients and investigators.
Safety Profile and Patient-Reported Outcomes
Beyond survival, daraxonrasib demonstrated a meaningfully better tolerability profile than chemotherapy. Grade 3 or higher treatment-related adverse events occurred in 43.6% of patients in the daraxonrasib arm compared with 57.5% in the chemotherapy arm. Treatment discontinuation due to adverse events was substantially lower with daraxonrasib, at 1.2% versus 11.2% for chemotherapy. At the data cut-off of 10 February 2026, 42% of patients on daraxonrasib remained on treatment, compared with just 14% in the chemotherapy group, an indicator of both tolerability and sustained clinical benefit.
Importantly, daraxonrasib also delayed deterioration in patient-reported pain and global quality of life, demonstrating clinically meaningful improvements in symptom control relative to chemotherapy. For a patient population that is often symptomatic at presentation, this dimension of the data carries particular weight.
Regulatory Pathway and What Comes Next
Revolution Medicines has confirmed its intention to submit the RASolute 302 data to global regulatory authorities, including the US Food and Drug Administration, as part of a future New Drug Application. Daraxonrasib holds several important regulatory designations: Breakthrough Therapy Designation from the FDA for previously treated metastatic PDAC in patients with KRAS G12 mutations, Orphan Drug Designation from both the FDA and the European Medicines Agency for pancreatic cancer, and a Commissioner’s National Priority Voucher under the FDA’s pilot programme.
On 1 May 2026, ahead of the ASCO presentation, the FDA granted Revolution Medicines permission to initiate an expanded access programme for daraxonrasib in patients with previously treated metastatic pancreatic cancer, providing early access to the drug for patients who may otherwise have no effective options.
The company’s pipeline extends beyond the second-line setting. RASolute 303, a registrational trial evaluating daraxonrasib as both monotherapy and in combination with chemotherapy in first-line metastatic PDAC, is underway. RASolute 304 is assessing daraxonrasib in the adjuvant setting following surgery. The company is also investigating daraxonrasib in combination with zoldonrasib, a KRAS G12D-selective inhibitor, with a registrational trial for the doublet combination planned for the second half of 2026. In parallel, daraxonrasib is being evaluated in non-small cell lung cancer in the Phase 3 RASolve 301 trial.
A Turning Point in Oncology
The response in the Chicago convention hall reflected something beyond the usual professional appreciation for positive trial data. Pancreatic cancer has been a field defined by incremental progress and persistent failure. The RASolute 302 data represent a genuine paradigm shift: the first large, randomised trial to demonstrate that targeting RAS directly in pancreatic cancer can not only be done but can deliver survival outcomes that dwarf what chemotherapy has achieved.
“This is the first RAS inhibitor evaluated in a large, randomised trial for patients with pancreatic cancer, and it demonstrates how important an impact these novel medicines are likely to have on the treatment of the disease,” said Dr Wolpin at the time of the ASCO presentation. “It is exciting to see that we may soon be able to help patients with metastatic pancreatic cancer in ways we haven’t been able to before, improving both survival and quality of life.”
With regulatory submissions now being prepared and an expanded access programme already under way, daraxonrasib looks set to become the new standard of care for second-line metastatic PDAC. For a disease in which progress has come so rarely, and so slowly, the standing ovation in Chicago felt less like a moment of enthusiasm and more like the sound of something finally changing.
