Tokyo – September 24, 2026 -- Astellas Pharma Inc. (TSE: 4503) has dosed the first patient in a Phase 3 study evaluating setidegrasib, an investigational KRAS G12D-targeted protein degrader, against docetaxel in previously treated non-small cell lung cancer (NSCLC) patients carrying the KRAS G12D mutation.
Trial targets patients who progressed on chemotherapy and checkpoint inhibitors
The randomized, open-label study will enroll approximately 356 patients across multiple countries whose locally advanced or metastatic NSCLC has progressed after platinum-based chemotherapy and checkpoint inhibitor therapy. Dual primary endpoints are progression-free survival, assessed by blinded independent central review, and overall survival.
No approved therapies exist for this molecularly defined subgroup
Roughly 5% of NSCLC patients carry the KRAS G12D mutation, according to Astellas. NSCLC accounts for approximately 80% of all lung cancer cases, which remains the leading cause of cancer-related death worldwide. Currently, patients whose disease progresses after initial treatment have no KRAS G12D-specific therapy and rely on standard chemotherapy options.
Second Phase 3 study launched within six months signals accelerated pipeline push
This NSCLC trial follows the April 2026 initiation of a Phase 3 study of setidegrasib in front-line pancreatic ductal adenocarcinoma (PDAC), marking Astellas' second Phase 3 study of the compound in under six months. The program supports Astellas' Corporate Strategic Plan, which targets the initiation of five or more Phase 3 or pivotal studies by fiscal year 2027.
Setidegrasib works by degrading the disease-driving KRAS G12D protein
Discovered through Astellas' in-house R&D, setidegrasib is designed to bring together the KRAS G12D protein and an E3 ligase, triggering selective degradation of the mutant protein via the cancer cell's own machinery. Early clinical evidence published in The New England Journal of Medicine in March 2026 demonstrated antitumor activity and a manageable safety profile in patients with KRAS G12D-mutated solid tumors.
Translational data on setidegrasib in pancreatic cancer to be presented at AACR conference
Astellas will present translational analyses from a Phase 1 study of setidegrasib in KRAS G12D-mutated PDAC patients at the AACR Conference on Pancreatic Cancer, running September 25–28, 2026, in San Diego. Lead author Wungki Park of Memorial Sloan Kettering Cancer Center will deliver a poster presentation on September 27 and an oral presentation on September 28, covering mechanisms of response, resistance, and potential combination strategies.
Hidenori Kitai of Hokkaido University's Faculty of Medicine said the Phase 3 study represents an important step toward building evidence for a molecularly defined patient population with limited options after standard therapies. Astellas Chief Research and Development Officer Tadaaki Taniguchi said the trial reflects continued progress in the compound's clinical development.
The safety and efficacy of setidegrasib have not been established for the indications under investigation, and there is no guarantee of regulatory approval.