FDA Grants Breakthrough Therapy Designation to Lilly’s Olomorasib for KRAS G12C Pancreatic Cancer

Eli Lilly and Company (NYSE: LLY) has received Breakthrough Therapy designation from the U.S. Food and Drug Administration for olomorasib (LY3537982), an investigational oral KRAS G12C inhibitor. The designation applies to olomorasib as a single-agent treatment for adults with advanced pancreatic cancer harboring a KRAS G12C mutation who have previously received at least one systemic therapy.

The Breakthrough Therapy program is designed to expedite the development and review of drugs that show early clinical evidence of substantial improvement over existing treatments for serious conditions. The FDA's decision was informed in part by preliminary results from the Phase 1/2 LOXO-RAS-20001 trial (NCT04956640), an open-label, multicenter study evaluating olomorasib in patients with advanced solid tumors driven by KRAS G12C mutations, including previously treated pancreatic cancer.

Second Breakthrough Designation

This is the second Breakthrough Therapy designation for olomorasib. In September 2025 the FDA granted the designation for olomorasib in combination with pembrolizumab as a first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation and PD-L1 expression ≥50%.

Clinical Context and Need

Pancreatic cancer remains one of the deadliest cancers: roughly 60,000 people in the United States are diagnosed each year, and the disease accounts for about 50,000 deaths annually. Patients with metastatic pancreatic cancer face a five-year survival rate below 5%. KRAS G12C mutations occur in approximately 1%–2% of pancreatic cancer cases, and there are currently no approved therapies that specifically target this mutation in pancreatic cancer.

Ongoing Development

Beyond the LOXO-RAS-20001 study, Lilly is evaluating olomorasib in global trials for KRAS G12C-mutant NSCLC, including SUNRAY-01 (NCT06119581) and SUNRAY-02 (NCT06890598). These programs will help define the safety and activity of olomorasib across tumor types and combinations.

Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said: "This designation reflects the early potential we're seeing with olomorasib in this setting and the critical need for new treatment options."

As an investigational oral agent, olomorasib remains under clinical evaluation, and its safety and efficacy profile will be determined through ongoing and future trials. Regulatory designation does not equate to approval, but it may facilitate more rapid development and review if subsequent data confirm meaningful clinical benefit.