Dr Nilo Azad presents early phase 1 results of a novel dual RAS inhibition strategy using zoldonrasib and daraxonrasib in patients with heavily pretreated metastatic pancreatic ductal adenocarcinoma harbouring KRAS G12D mutations. With limited treatment options and poor survival outcomes in this setting, targeting KRAS G12D represents a major unmet need in pancreatic cancer therapy.

The combination of these oral RAS(ON) inhibitors is designed to enhance pathway suppression, deepen responses, and delay resistance compared with single agent approaches. Initial findings show encouraging clinical activity alongside a manageable safety profile, with most treatment related adverse events being low grade and consistent with the mechanism of action.

Although some grade 3 or higher toxicities were observed, discontinuation rates were low, and overall treatment exposure remained high, supporting tolerability of the regimen.

These results highlight the potential of dual RAS targeting as a new therapeutic strategy in KRAS driven pancreatic cancer and have led to the initiation of a global phase 3 trial to further evaluate this combination in earlier lines of treatment.