Conferences / ASCO 06/18/2026

Phase 3 RASolute 302 Trial: Groundbreaking Data for Daraxonrasib in mPDAC

Close-up portrait of a professional medical expert with a confident expression, wearing a striped shirt, against a neutral background. Brian Wolpin MD MPH Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD

Key Points

  • In the RASolute 302 study, daraxonrasib doubled survival with favorable safety compared with standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (mPDAC) in the second-line setting.
  • Rash is the most notable side effect with daraxonrasib, although prophylaxis with strategies similar to those used with EGFR inhibitors can help manage side effects.
  • Daraxonrasib is effective regardless of RAS mutation status, although sequencing is still important to identify other potential drivers.

ASCO 2026 Presentation for RASolute 302

On the Oncology Brothers podcast, cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, spoke with the first author on the RASolute 302 study Brian Wolpin, MD, MPH, of Dana-Farber Cancer Institute, to review the groundbreaking data for daraxonrasib that he presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026).

More than 90% of patients with pancreatic cancer carry a RAS mutation, the most common of which are G12D, G12V, and G12R. Existing KRAS inhibitors like sotorasib and adagrasib target KRAS G12C–mutated tumors by locking inactive mutant KRAS proteins in the inactive state. In comparison, daraxonrasib is a multiselective RAS(ON) inhibitor that disrupts active RAS proteins in both RAS–mutated and RAS–wild-type mPDAC. 

RASolute 302 Efficacy Findings

The phase 3 RASolute 302 study compared daraxonrasib with standard cytotoxic chemotherapies as second-line treatment for adult patients with mPDAC and Eastern Cooperative Oncology Group Performance Status of 0 or 1. Enrollment criteria required one prior fluoropyrimidine-based or gemcitabine-based chemotherapy regimen in the metastatic setting and documented RAS mutation testing. 

The study randomized 248 patients to daraxonrasib and 252 to chemotherapy. The primary end points were overall survival (OS) and progression-free survival (PFS) in patients with RAS G12 mutations. Key secondary end points included OS and PFS in the overall population and objective response rate (ORR) in the RAS G12 and overall populations. At the time of the ASCO 2026 presentation, the median follow-up was 8.5 months. 

In the RAS G12–mutated subgroup, the median OS was 13.2 months (95% CI, 10-not estimable [NE]) with daraxonrasib and 6.6 months (95% CI, 5.4-8.2) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.54; P < .0001). The median PFS was 7.3 months (95% CI, 6.3-8.1) with daraxonrasib and 3.5 months (95% CI, 2.9-3.8) with chemotherapy (HR, 0.45; 95% CI, 0.34-0.59; P < .0001). The ORRs in the daraxonrasib and chemotherapy groups were 33.2% (95% CI, 27-39.9) and 11.8% (95% CI, 7.8-16.8), respectively.

In the overall population, the median OS was 13.2 months (95% CI, 10-NE) with daraxonrasib and 6.7 months (95% CI, 5.8-8.0) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.53; P < .0001). The median PFS was 7.2 months (95% CI, 5.7-7.5) with daraxonrasib and 3.6 months (95% CI, 2.9-4.2) with chemotherapy (HR, 0.49; 95% CI, 0.38-0.64; P < .0001). The ORRs were 31.6% (95% CI, 25.8-38) with daraxonrasib and 11.2% (95% CI, 7.5-15.9) with chemotherapy.

Safety Profile of Daraxonrasib

Authors reported that 43.6% of the daraxonrasib arm and 57.5% of the chemotherapy arm experienced grade 3 or higher treatment-related adverse events (TRAEs). The most common grade 3 or higher TRAEs with daraxonrasib were rash (13.7%) and stomatitis (12%), and with chemotherapy were neutrophil decrease (18.2%) and anemia (16.4%). Serious TRAEs were reported in 10.8% of patients on daraxonrasib and 18.7% of patients on chemotherapy. TRAEs leading to discontinuation occurred in 1.2% of patients on daraxonrasib versus 11.2% of patients on chemotherapy. 

During the trial, around one-third of patients required a dose reduction, almost entirely due to rash events, said Dr. Wolpin. The researchers incorporated rash prophylaxis with antibiotics and steroid creams, which were escalated to stronger antibiotics and retinoid creams if rash persisted. Alongside these strategies, Dr. Wolpin recommended oncologists partner with local dermatology specialists and counsel patients to limit sun exposure to help manage rash side effects. 

Diarrhea, nausea, and vomiting were also common side effects of daraxonrasib, although most events were low-grade and standard management strategies or dose holds were typically effective, said Dr. Wolpin. 

Patient Selection for Daraxonrasib

Given the profound benefit seen with daraxonrasib regardless of RAS mutation status, Dr. Rahul Gosain questioned whether it is appropriate to use daraxonrasib without mutation testing results. While Dr. Wolpin supported the use of daraxonrasib for all patients, he felt that mutation testing on biopsy samples should still be performed in all patients, as some may carry additional non-RAS driver mutations. Identifying these other drivers may become important in the future as trials explore novel combinations of RAS inhibitors and other agents. 

The only PDAC population where Dr. Wolpin might prefer to start with other therapies before daraxonrasib would be the small proportion of patients without RAS mutations that carry other oncogenic drivers with approved targeted therapies, such as NTRK fusions, NRG1 fusions, or BRAF V600E mutation.