Clinical Summary: 

• Design/Population: The phase 3 RASolute 302 trial randomized patients with second-line metastatic pancreatic ductal adenocarcinoma to receive daraxonrasib or investigator’s choice of standard cytotoxic chemotherapy.

• Key Outcomes: Daraxonrasib significantly improved survival versus chemotherapy and was generally well tolerated.
• Clinical Relevance: Daraxonrasib may establish a new standard of care for second-line metastatic pancreatic ductal adenocarcinoma, offering a targeted oral option with improved efficacy and a manageable safety profile across patients with and without identified RAS mutations.

Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses results from the phase 3 RASolute 302 trial which demonstrated that daraxonrasib, a first-in-class RAS(ON) multi-selective inhibitor, significantly improved both overall survival (OS) and progression-free survival (PFS) compared with standard chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma. 

Benefits were observed in patients with RAS G12 mutations as well as in the overall study population, while maintaining a manageable safety profile with fewer severe adverse events and treatment discontinuations. 

Dr Wolpin presented these results in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript:

I'm Brian Wolpin. I'm the director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute. At ASCO, we are presenting results from the RASolute 302 clinical trial. This is a randomized phase 3 clinical trial for patients with previously treated metastatic pancreatic cancer where we are evaluating a drug, a new medicine called Daraxonrasib,and comparing that to chemotherapy, which is the standard of care in that setting. 

So, this is a randomized study. It was done because chemotherapy does not work as well as we would like for patients with pancreatic cancer. However, over 90% of pancreatic cancers carry an activating mutation in the RAS oncogene; in particular, KRAS at codon 12 is the most common. And so Daraxonrasib is a drug that blocks the on version, the GTP-bound version, of RAS, including KRAS, and it binds both to the mutant version and also to the wild-type version.

In a previous study, a phase 1-2 trial, Daraxonrasib has demonstrated promising clinical activity and tolerable safety in patients with previously treated metastatic pancreatic cancer. Given those data, the randomized phase 3 RASolute 302 trial was designed and then run. In that study, approximately 500 patients were randomized one-to-one to receive Daraxonrasib or chemotherapy. Patients must have had previously treated metastatic pancreatic cancer, and they could either have a RAS mutation or not. The trial actually allowed all patients to enroll with previously treated metastatic pancreatic cancer. The clinical trial then looked at a primary endpoint of overall survival and a co-primary endpoint of progression-free survival and then also looked at objective response rate and patient-reported outcomes. 

The study demonstrated a statistically significant improvement in survival for patients who received Daraxonrasib compared to chemotherapy. The median overall survival was 13.2 months in the group who received Daraxonrasib and 6.7 months in the group who received chemotherapy. In addition, there was a statistically significant improvement in progression-free survival for the entire population in the study. Finally, for objective response rate, there was an improvement in objective response rate, a little over 30% objective response rate to Daraxonrasib and around 11% for chemotherapy, so a substantial increase in the Daraxonrasib. 

From the patient-reported outcomes data, what we saw is that there was a delay in the time to worsening of either pain or a decrease in quality of life in the patients who received Daraxonrasib compared to chemotherapy. When we looked at the side effects that these medicines cause, the main side effects from Daraxonrasib were rash and mucositis. And then chemotherapy, that's quite well known. We've been using that for many years, a variety of different side effects, including blood count suppression, peripheral neuropathy, nausea, diarrhea, and others. Overall, there were less treatment reductions and less treatment discontinuations for patients who received Daraxonrasib compared to chemotherapy.

So, in aggregate, in summary, Daraxonrasib in the RASolute 302 study met the primary endpoint and all key secondary endpoints in patients with previously treated metastatic pancreatic cancer, including improvements in overall survival, progression-free survival, response rate, and patient-reported outcomes. It demonstrated a manageable safety profile, and this drug, we hope, will provide a new standard of care for patients with previously treated metastatic pancreatic cancer.

Source:

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. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA5.