Japanese pharmaceutical company Astellas Pharma Inc (TSE:4503) announced on Wednesday that the first patient has been dosed in a Phase 3 study evaluating setidegrasib, a novel, investigational KRAS G12D-targeted protein degrader, versus docetaxel in people with KRAS G12D-mutated locally advanced (unresectable) or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on or after initial platinum-based chemotherapy and checkpoint inhibitor therapy (CPI).

Setidegrasib is an investigational targeted protein degrader designed to degrade and eliminate the disease-driving KRAS G12D protein. By removing this protein, setidegrasib may help disrupt cancer cell signalling and destroy cancer cells. This Phase 3 study in previously treated NSCLC builds on early clinical evidence published in The New England Journal of Medicine in March 2026, which demonstrated anti-tumor activity and a manageable safety profile in patients with KRAS G12D-mutated solid tumours, supporting the proposed mechanism of action of setidegrasib.

A Phase 3 study of setidegrasib in front-line pancreatic ductal adenocarcinoma (PDAC) was launched in April 2026.

Astellas plans to present translational analyses from the Phase 1 study of setidegrasib in patients with KRAS G12D-mutated PDAC at the upcoming AACR Conference on Pancreatic Cancer, providing further insight into mechanisms of response, resistance and potential rational combination approaches in pancreatic cancer.