Astellas initiates Phase 3 trial of setidegrasib, a KRAS G12D-targeted protein degrader, in first-line metastatic pancreatic cancer.
Written By: Mahathi Palivela, PharmD
Reviewed By: Pharmacally Editorial Team
Astellas Pharma Inc. has dosed the first patient in a Phase 3 registrational study of setidegrasib (ASP3082) for KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma (PDAC). The trial evaluates setidegrasib in combination with mFOLFIRINOX or NALIRIFOX as first-line treatment. KRAS G12D mutations occur in about 40% of PDAC cases and currently lack targeted therapies.
Setidegrasib is an investigational protein degrader designed to selectively bind KRAS G12D and trigger its degradation via E3 ligase recruitment. Phase 1 (NCT05382559) data showed target degradation consistent with this mechanism, supporting advancement into late-stage development.
The randomized, double-blind, placebo-controlled Phase 3 study will enroll over 600 patients globally. The primary endpoint is overall survival, with progression-free survival and safety as key secondary endpoints.
Astellas’ R&D head, Tadaaki Taniguchi, stated that advancing a KRAS G12D-targeted degrader into Phase 3 reflects progress against a historically difficult oncogenic driver and underscores the company’s investment in targeted protein degradation.
Setidegrasib remains investigational, and its safety and efficacy are not yet established.
References
Astellas Doses First Patient in Phase 3 Study of setidegrasib (ASP3082) for KRAS G12D-mutated Metastatic Pancreatic Ductal Adenocarcinoma, April 15,2026 https://newsroom.astellas.com/2026-04-15-astellas-doses-first-patient-in-phase-3-study-of-setidegrasib-for-kras-g12d-mutated-metastatic-pancreatic-ductal-adenocarcinoma
A Study of ASP3082 in Adults with Advanced Solid Tumors, ClinicalTrials.gov ID NCT05382559 https://clinicaltrials.gov/study/NCT05382559
About the Writer
Mahathi Palivela is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication .