An Unexpected Sotorasib Setback Creates an Opening for KRAS Competitors

Amgen’s first-in-class KRAS(G12C) inhibitor, sotorasib, recently encountered an unexpected but significant regulatory setback with the FDA at its October 5th Oncologic Drugs Advisory Committee Meeting (ODAC). Based on the strength of the biological mechanism and initially reported clinical data, full approval for sotorasib had widely been expected in the industry. However, the FDA ODAC voted 10 to 2 that progression-free survival (PFS), the key endpoint for comparing sotorasib to docetaxel chemotherapy, could not be reliably interpreted in the pivotal CodeBreaK200 (NCT04303780) study for KRASG12C+ in late-stage NSCLC. What happened, and what does it mean for KRAS inhibitors?