The FDA granted breakthrough therapy designation to Eli Lilly’s next-generation KRAS G12C inhibitor olomorasib for patients with advanced pancreatic cancer whose disease is KRAS G12C–mutant and who have received at least one prior systemic therapy. The decision is tied to preliminary results from the phase 1/2 LOXO-RAS-20001 trial (NCT04956640), evaluating olomorasib monotherapy in KRAS G12C-driven advanced solid tumors. Lilly said the regulatory call reflects early potential in a setting where no approved therapies specifically target KRAS G12C mutations in pancreatic cancer. The designation also marks the second breakthrough designation for olomorasib, following an earlier FDA action in September 2025 for the agent in combination with pembrolizumab (Keytruda) in first-line KRAS G12C–mutant non–small cell lung cancer. Patients in LOXO-RAS-20001 were required to have ECOG 1 or less, adequate organ function, resolved prior-treatment adverse effects, and measurable disease per RECIST 1.1, with KRAS G12C confirmed via FDA-approved testing using circulating tumor DNA or tumor tissue.