New clinical trial results presented at the 2026 ESMO GI Cancers Congress suggest that zoldonrasib-based treatments may significantly improve outcomes for patients with KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma (PDAC).
In previously untreated patients, zoldonrasib combined with modified FOLFIRINOX achieved an objective response rate of 82% and a disease control rate of 96%. When combined with gemcitabine and nab-paclitaxel, the response rate was 61% with a 90% disease control rate. Severe treatment-related side effects were mainly low neutrophil counts but were considered manageable.
In patients whose cancer had already been treated, the oral combination of zoldonrasib and daraxonrasib also showed encouraging results. Response rates reached 50% in second-line treatment and 47% in later-line therapy, with median progression-free survival of 9.6 and 7.6 months, respectively. Serious side effects occurred in 35% of patients, while treatment discontinuation was uncommon.
Based on these findings, Revolution Medicines is advancing both treatment approaches into phase 3 clinical trials. The results also build on earlier phase 3 data showing that daraxonrasib alone doubled overall survival compared with chemotherapy in previously treated pancreatic cancer, leading to FDA Breakthrough Therapy and Orphan Drug designations.