Dr Pant on Landmark Efficacy Data With Daraxonrasib in Previously Treated Metastatic PDAC

"These data are going to be practice changing...not only for those of us in academic medicine, but for our community oncologists who treat a majority of the patients with pancreatic cancer."

Shubham Pant, MD, MBBS, a professor in the Department of Gastrointestinal (GI) Medical Oncology and director of Clinical Research at The University of Texas MD Anderson Cancer Center, discussed groundbreaking results from the phase 3 RASolute 302 trial (NCT06625320) evaluating daraxonrasib (RMC-6236) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC)

RASolute 302 is an ongoing, global, randomized, controlled trial enrolling patients with previously treated PDAC harboring various RAS mutations, such as G12D, G12V, and G12R, as well as those with no identified RAS mutation.

Data from an interim analysis of RASolute 302 revealed that daraxonrasib generated statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) vs standard chemotherapy. In the intention-to-treat population, patients receiving daraxonrasib achieved a median OS of 13.2 months, nearly doubling the 6.7 months observed in the chemotherapy arm (HR, 0.40; P < .0001). Importantly, daraxonrasib was generally well tolerated with a manageable safety profile, and no new safety signals were reported during the trial.

These data, which will be presented at the 2026 ASCO Annual Meeting, are poised to be practice-changing for both academic and community oncologists, who treat the majority of patients with pancreatic cancer, Pant stated. He characterized these findings as historic, noting that the field has not seen data this impactful since the comparison of FOLFIRINOX against gemcitabine more than a decade ago.

The broader development of daraxonrasib also includes its use in the frontline setting. Complementary data from phase 1/2 trials (NCT05379985 and NCT06445062) have explored daraxonrasib as a monotherapy and in combination with nab-paclitaxel (Abraxane) and gemcitabine. The agent is also under investigation alongside chemotherapy in frontline metastatic PDAC in the phase 3 RASolute-303 trial (NCT07491445).

Regarding its regulatory status, daraxonrasib previously received FDA breakthrough therapy and orphan drug designations for patients with previously treated metastatic PDAC harboring KRAS G12 mutations. Additionally, on May 1, 2026, the FDA issued a “safe to proceed” letter permitting the initiation of an expanded access treatment protocol (EAP) for daraxonrasib (RMC-6236) for patients with previously treated metastatic PDAC.

Pant concluded that the emergence of daraxonrasib marks a new era in precision medicine for PDAC, offering a potent alternative to traditional cytotoxic regimens.