New data show that zoldonrasib (RMC-9805), an oral RAS G12D-targeted therapy, produced promising results in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) carrying a RAS G12D mutation.
In previously untreated patients, zoldonrasib combined with modified FOLFIRINOX achieved an objective response rate of 82%, while the combination with gemcitabine plus nab-paclitaxel reached 61%. Disease control rates were 96% and 90%, respectively.
In previously treated patients, the chemotherapy-free combination of zoldonrasib and daraxonrasib achieved response rates of 50% in second-line treatment and 47% in third-line or later treatment. Median progression-free survival was 9.6 months and 7.6 months, respectively.
The treatments showed manageable safety profiles. No treatment-related deaths were reported, and few patients stopped treatment because of side effects.
Based on these encouraging results, Revolution Medicines has launched two global phase 3 trials to evaluate zoldonrasib with standard chemotherapy and a chemotherapy-free combination of zoldonrasib plus daraxonrasib as first-line treatment for metastatic PDAC.