Phase 3 setidegrasib (ASP3082) KRAS G12D–targeted protein degrader vs docetaxel

Astellas Pharma Global Development is running this randomized, open-label Phase 3 study comparing setidegrasib (ASP3082) with docetaxel in adults with locally advanced unresectable or metastatic NSCLC harboring KRAS G12D (~5% of NSCLC). Setidegrasib is a KRAS G12D–selective protein degrader designed to eliminate the mutant KRAS protein rather than simply inhibit signaling, positioning it as a differentiated approach among KRAS-directed agents. Participants must have progressed on or after platinum-based chemotherapy and checkpoint inhibitor therapy, and have had no more than two prior systemic lines; key exclusions include actionable alternative drivers and uncontrolled/symptomatic CNS disease. The primary efficacy focus is progression-free survival (and overall survival), with crossover from docetaxel to setidegrasib allowed after progression—commercially important because docetaxel (with or without ramucirumab in practice) remains a common later-line option when targeted therapies aren’t available, but durability is limited.