Pancreatic ductal adenocarcinoma (PDAC) continues to remain one of the most aggressive and difficult-to-treat malignancies, with limited therapeutic options and poor long-term survival outcomes in the metastatic setting. Despite advances in chemotherapy, treatment benefits in previously treated metastatic PDAC patients remain modest, underscoring the need for novel targeted approaches. RAS mutations are highly prevalent in pancreatic cancer, making RAS-directed therapies an important area of clinical development. 

At ASCO 2026, topline results from the analysis of the Phase III trial (RASolute 302) demonstrated that daraxonrasib significantly improved survival outcomes compared with standard chemotherapy in previously treated metastatic PDAC patients.

The results presented were as follows:

Efficacy outcomes:

• OS: Median OS was 13.2 months with daraxonrasib vs 6.7 months with chemotherapy, reducing the risk of death by 60% (HR: 0.40; p < 0.0001).

• PFS: Median PFS was 7.2 months vs 3.6 months, with a 51% reduction in the risk of progression or death (HR: 0.49; p < 0.0001).

• ORR: Response rates were 31.6% with daraxonrasib compared to 11.2% with chemotherapy.

• RAS G12 Subgroup: Daraxonrasib achieved superior outcomes, with OS of 13.2 vs 6.6 months, PFS of 7.3 vs 3.5 months, and ORR of 33.2% vs 11.8%. 

Safety results:

• Grade ≥3 TRAEs occurred in 43.6% of patients receiving daraxonrasib vs 57.5% receiving chemotherapy. 

• The most common (≥10%) Grade ≥3 TRAEs were rash (13.7%) and stomatitis (12.0%) for daraxonrasib; neutrophil decrease (18.2%) and anemia (16.4%) for chemotherapy. 

• TRSAEs occurred in 10.8% of patients receiving daraxonrasib vs 18.7% receiving chemotherapy.

• Discontinuation due to TRAEs occurred in 1.2% of patients for daraxonrasib vs 11.2% for chemotherapy.

KOL insights

“The widely anticipated results of this study indicate that daraxonrasib represents a clear and highly meaningful step forward for patients with pancreatic cancer who have progressed on prior treatment, typically chemotherapy. This new approach is considered a significant advance for the field and is expected to be practice-changing for physicians while improving care for patients with previously treated metastatic pancreatic cancer.”– Brian M. Wolpin, MD, MPH.

“In this pivotal trial, daraxonrasib as a targeted medicine delivered a dramatic improvement in overall survival in patients with previously treated metastatic pancreatic cancer compared to standard of care chemotherapy, consistent with earlier findings. These results represent a potentially transformative advance for patients and underscore daraxonrasib’s potential to redefine the treatment landscape.”– Mark A. Goldsmith, MD, PhD.

Conclusion- 

Daraxonrasib demonstrated unprecedented improvements in OS, PFS, and ORR compared with chemotherapy in patients with 2L mPDAC, irrespective of tumor RAS mutation status. The therapy was generally well tolerated, with a manageable safety profile, fewer severe adverse events and treatment discontinuations, and no new safety signals. These landmark findings position daraxonrasib as a potential new standard of care for patients with 2L mPDAC.