BOSTON — Researchers from Dana-Farber Cancer Institute presented phase I/II trial results for the drug zoldonrasib in patients with KRAS G12D-mutated metastatic pancreatic cancer at the ESMO Gastrointestinal Cancers Congress on July 3, 2026. The study evaluated zoldonrasib in a multicenter setting.

Zoldonrasib is designed to selectively inhibit the KRAS G12D mutation. Approximately 90% of pancreatic cancers harbor a KRAS mutation, and roughly 40% of these carry the KRAS G12D subtype. The five-year survival rate for metastatic pancreatic cancer is approximately 3%.

The study enrolled 81 patients with previously untreated metastatic pancreatic cancer who had a KRAS G12D mutation. These patients were recruited at multiple cancer centers in the United States. Of the enrolled patients, 41 received zoldonrasib in combination with modified FOLFIRINOX, while 40 patients received zoldonrasib alongside gemcitabine and nab-paclitaxel.

Objective response rates reached 82% among patients treated with zoldonrasib plus modified FOLFIRINOX. For those receiving zoldonrasib plus gemcitabine and nab-paclitaxel, objective response rates were 61%. Disease control was achieved in 96% of patients in the modified FOLFIRINOX group and 90% in the gemcitabine and nab-paclitaxel group.

Every evaluable patient in the study experienced at least a 50% reduction in circulating tumor DNA carrying the KRAS G12D mutation. Complete clearance of detectable mutant circulating tumor DNA was observed in 47% of evaluable patients receiving modified FOLFIRINOX. This clearance rate was 71% in evaluable patients treated with gemcitabine plus nab-paclitaxel.

Grade 3 or higher treatment-related adverse events occurred in 61% of patients receiving zoldonrasib plus modified FOLFIRINOX. In the group treated with zoldonrasib plus gemcitabine/nab-paclitaxel, 80% experienced grade 3 or higher treatment-related adverse events. No treatment-related deaths occurred during the study.

Teresa Macarulla, Head of the Medical Oncology Department at Hospital Clínic Barcelona, said: "The emergence of therapies designed specifically against KRAS G12D represents one of the most promising areas of research in pancreatic cancer today." She added: "For many years, this mutation was considered impossible to target, making these early findings particularly important."

A Phase III trial, designated RASolute 305, has been launched to compare zoldonrasib plus chemotherapy with placebo plus chemotherapy. Macarulla said: "If these findings are confirmed, this approach could represent an important advance towards more personalised treatment for pancreatic cancer." She also said: "It could also be explored in earlier stages of disease, where greater tumor shrinkage before surgery may improve patient outcomes."