Favorable phase 3 results for pancreatic cancer drug daraxonrasib heralded as a 'grand slam'| ASCO 2026

An open-label, phase 3 trial of a drug that targets a protein once deemed undruggable showed statistically significant improvement in the primary end points of overall survival and progression-free survival among patients with metastatic pancreatic cancer previously treated with one line of therapy, according to results presented today at a plenary session of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago

Patients who were randomly assigned to be treated with daraxonrasib had a median overall survival of 13.2 months compared with 6.6 months among those treated with an investigator’s choice of chemotherapy. The difference in progression-free survival was similar: a median of 7.3 months in the daraxonrasib group compared with 3.5 months in the chemotherapy group.

Those were the results for patients with the most common types of mutations in the RAS gene, which are grouped under the heading RAS G12. The results were similar when all the patients in the trial were included in the researchers’ analysis.

“I've heard this study described as a home run a lot. I would actually say it's a grand slam. It is much more than a home run,” said Julie R. Gralow, M.D., ASCO’s chief medical officer, during a news conference where the study’s results were presented by lead investigator Brian M. Wolpin, M.D., M.P.H., of the Dana-Farber Cancer Institute in Boston on an embargoed basis.

“Having treated pancreatic cancer for 16 years, I actually started crying in clinic. This is such an incredibly impactful study for our patients,” said Rachna Shroff, M.D., M.S., the ASCO-selected commentator on the study and chief of the Division of Hematology/Oncology at the University of Arizona Cancer Center in Tucson.

Researchers have long known that proteins generated by mutations in the RAS gene family have cancer-causing properties, but the shape and other characteristics of the aberrant proteins have made them elusive, undruggable targets for therapies that would kill or disable them. Shubham Pant, M.D., M.B.B.S., of The University of Texas MD Anderson Cancer Center in Houston and one of the study’s investigators, compared the protein to a shiny ball. “You can’t stick anything to it. It just kind of slides off,” Pant said in a recent interview with Managed Healthcare Executive. Daraxonrasib gets around that problem, Pant explained, by binding to a cellular chaperone called cyclophilin A that he said is like “molecular glue.” As a result, the daraxonrasib adheres to the RAS protein, leading to tumor cell death. Moreover, the sticky complex is a “pan-RAS inhibitor,” Pant said, making it effective against cells with RAS genes harboring various mutations. Data presented by Wolpin suggest that the drug is also effective against pancreatic cancer cells that don’t have RAS mutations.

The results of the phase 3 trial, RASolute 302, shared by Wolpin were hailed but came as a surprise. Wolpin is the lead author of an article describing positive results for daraxonrasib in a phase 1 trial; the article was published in the New England Journal of Medicine earlier in June. Moreover, the Wall Street Journal, the New York Times and other prominent news outlets have published articles showcasing daraxonrasib.

Wolpin, Pant and their fellow RASolute 302 investigators enrolled 500 patients with metastatic pancreatic cancer at 59 sites in six countries. The study participants had all been treated with one prior fluoropyrimidine- or gemcitabine-based regimen, the standard first-line therapy for pancreatic cancer. All study participants’ cancers were tested for RAS mutations, but participants did not need to have mutations to be enrolled. A large majority (459 of 500) of the study participants had the RAS G12 mutations, the most common in pancreatic cancer, and overall survival and progression-free survival in that RAS G12 population were the study’s primary end points. The researchers randomly assigned the study participants to either daraxonrasib (a 300-milligram pill once a day) or 1 of 4 chemotherapy regimens selected by the investigator. The data cutoff date was Feb. 10, 2026. Revolution Medicines, the biotech company developing daraxonrasib, sponsored the study.

As reported by Wolpin, the data all point in daraxonrasib’s favor in both the RAS G12 group and the overall group. In addition to overall survival and progression-free survival, the overall response rate was approximately 3 times higher in patients treated with daraxonrasib than in those treated with chemotherapy (33.2% vs. 11.8% in the RAS G12 group), according to the results Wolpin presented at the news conference.

The data on side effects and patient-reported quality of life shared by Wolpin at the news conference also painted a favorable picture of daraxonrasib, although one patient in the daraxonrasib group died from treatment-related pneumonia. According to Wolpin, 87 (36.1%) of the patients in the daraxonrasib group had side effects that led to dose reduction compared with 123 (57.5%) in the chemotherapy group. The most common (5% or more) side effects leading to dose reduction in patients treated with daraxonrasib were rash and stomatitis (inflammation of the lining of the mouth). In those treated with chemotherapy, the side effects were those commonly seen in chemotherapy, including neutropenia, fatigue, diarrhea and peripheral neuropathy.

Wolpin and his colleagues used a questionnaire about pain and other issues to measure quality of life. Calculations of “time to deterioration” — when those answers on questionnaires revealed a significant worsening — favored daraxonrasib.