Indianapolis, August 3, 2026
Eli Lilly and Company announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olomorasib as a monotherapy for adults with advanced pancreatic cancer harboring a KRAS G12C mutation who have received at least one prior systemic therapy. The mutation must be identified using an FDA-approved test. Olomorasib is an investigational, oral, potent and highly selective next-generation KRAS G12C inhibitor being developed across multiple KRAS G12C-driven cancers. The latest regulatory milestone represents the second Breakthrough Therapy designation for olomorasib and highlights Lilly’s efforts to advance precision oncology treatments for difficult-to-treat malignancies with significant unmet medical need.
FDA Designation Advances KRAS G12C-Targeted Therapy
The FDA Breakthrough Therapy designation is intended to expedite the development and regulatory review of medicines for serious conditions when preliminary clinical evidence indicates that a therapy may provide substantial improvement over available treatments on clinically significant endpoints. The designation for olomorasib is based on encouraging preliminary results from LOXO-RAS-20001, an open-label, multicenter Phase 1/2 clinical study, evaluating patients with KRAS G12C-mutant advanced solid tumors. The supporting population includes patients with advanced pancreatic cancer who had received at least one previous systemic treatment. The study incorporates a Phase 1a dose-escalation component evaluating olomorasib monotherapy and Phase 1b dose-expansion and optimization cohorts investigating the candidate both alone and in combination with other treatments. The designation may provide Lilly with more intensive FDA guidance during development as the company continues evaluating olomorasib’s clinical potential.
Olomorasib Targets Major Unmet Need in Pancreatic Cancer
Pancreatic cancer remains one of the most difficult-to-treat malignancies, with approximately 60,000 people diagnosed in the United States annually and an estimated 50,000 deaths projected each year. Outcomes are particularly poor for metastatic disease, where the five-year survival rate remains below 5%. KRAS mutations are present in approximately 90% of pancreatic cancers, while the specific KRAS G12C mutation occurs in around 1% to 2% of patients. Lilly noted that there are currently no approved therapies specifically targeting KRAS G12C-mutant pancreatic cancer, creating a substantial unmet need for molecularly targeted treatment approaches. Olomorasib, also known as LY3537982, was specifically designed to target the KRAS G12C protein and has pharmacokinetic characteristics intended to provide high predicted target occupancy and potency when administered either as monotherapy or in combination. The candidate remains investigational, and further clinical studies will be required to establish its safety and efficacy.
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Lilly Expands Olomorasib Across KRAS G12C-Driven Cancers
The pancreatic cancer designation represents olomorasib’s second FDA Breakthrough Therapy designation. In September 2025, the FDA granted the designation to olomorasib in combination with pembrolizumab for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying a KRAS G12C mutation and PD-L1 expression of at least 50%, as determined by FDA-approved tests. Lilly is currently evaluating olomorasib across several KRAS G12C-mutant cancers. In addition to the Phase 1/2 LOXO-RAS-20001 study, the candidate is being investigated in the pivotal SUNRAY-01 global registrational study, which is evaluating olomorasib with pembrolizumab, with or without chemotherapy, as first-line treatment for KRAS G12C-mutant advanced NSCLC. The SUNRAY-02 global study is also investigating olomorasib with standard-of-care immunotherapy in patients with resected or unresectable KRAS G12C-mutant NSCLC. The latest FDA designation strengthens the regulatory profile of Lilly’s next-generation targeted therapy while expanding its potential role beyond lung cancer into KRAS G12C-mutant pancreatic cancer. Continued clinical development will determine whether olomorasib can translate its preliminary activity into a new precision medicine option for patients with this aggressive and molecularly defined form of pancreatic cancer.
Source: Eli Lilly press release
