Eli Lilly and Company has received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for olomorasib as a monotherapy for the treatment of adults with advanced pancreatic cancer carrying a KRAS G12C mutation who have received at least one prior systemic therapy.

The designation is intended to accelerate the development and regulatory review of medicines that demonstrate the potential to offer substantial improvements over existing therapies for serious diseases. Olomorasib is an investigational, highly selective next-generation inhibitor targeting the KRAS G12C mutation, a known cancer-driving genetic alteration.

This marks the second Breakthrough Therapy designation for olomorasib. The therapy had previously received the designation in combination with Keytruda (pembrolizumab) for the first-line treatment of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harbouring KRAS G12C mutations and high PD-L1 expression.

The latest designation is supported by preliminary findings from the ongoing Phase 1/2 LOXO-RAS-20001 clinical trial, an open-label, multicentre study evaluating the safety, tolerability and early efficacy of olomorasib in patients with KRAS G12C-mutant advanced solid tumours, including pancreatic cancer.

Pancreatic cancer remains one of the most challenging malignancies to treat, with approximately 60,000 new cases diagnosed annually in the United States and an estimated 50,000 deaths each year. Patients with metastatic disease have a five-year survival rate of less than five percent, while those with KRAS G12C-mutant tumours often experience poorer outcomes than patients without the mutation. Currently, there are no FDA-approved therapies specifically targeting KRAS G12C-mutant pancreatic cancer.

Commenting on the development, Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said the designation highlights both the encouraging early clinical activity of olomorasib and the urgent need for new treatment options for patients with advanced pancreatic cancer. He added that receiving Breakthrough Therapy designations in both pancreatic and lung cancers reinforces the therapy's potential across KRAS G12C-driven tumours.

Olomorasib is an investigational oral therapy designed to achieve high target occupancy and potent inhibition of the KRAS G12C protein. KRAS mutations account for nearly 85 percent of RAS-associated cancers, while KRAS G12C mutations occur in approximately 1-2 percent of pancreatic cancer cases.

Beyond the LOXO-RAS-20001 study, Lilly is evaluating olomorasib in multiple global clinical programmes, including the pivotal SUNRAY-01 trial investigating the therapy in combination with pembrolizumab, with or without chemotherapy, for first-line treatment of advanced KRAS G12C-mutant NSCLC, and the SUNRAY-02 study assessing its use alongside standard immunotherapy in patients with resected or unresectable KRAS G12C-mutant NSCLC.

The latest regulatory milestone strengthens Lilly's oncology pipeline as the company advances targeted therapies aimed at addressing significant unmet needs in KRAS-driven cancers.