The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Eli Lilly’s investigational drug olomorasib as a monotherapy for the treatment of adult patients with advanced pancreatic cancer carrying a KRAS G12C mutation who have received at least one prior systemic therapy. Patients must be identified using an FDA-approved diagnostic test.
This marks the second Breakthrough Therapy designation for olomorasib, a potent and highly selective next-generation inhibitor of KRAS G12C. The first was granted in September 2025 for olomorasib in combination with the anti-PD-1 therapy pembrolizumab as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) harbouring a KRAS G12C mutation and PD-L1 expression of 50% or higher, as determined by FDA-approved diagnostic tests.
The FDA’s Breakthrough Therapy designation is intended to accelerate the development and review of drugs for serious conditions when preliminary clinical evidence suggests they may offer substantial improvements over already available therapies.
Growing evidence suggests that patients with KRAS G12C-mutant pancreatic cancer have poorer outcomes than those without the mutation. Currently, there are no approved targeted therapies for this patient population.
“Pancreatic cancer has historically been one of the most difficult-to-treat cancers and people whose tumours harbour a KRAS G12C mutation face limited options once their disease progresses,” said Jacob Van Naarden, executive vice president, and president of Lilly Oncology.
“This Breakthrough Therapy designation reflects the early potential we’re seeing with olomorasib in this setting and the critical need for new treatment options. With now two Breakthrough Therapy designations across pancreatic and lung cancers, olomorasib continues to demonstrate broad potential clinical evidence across KRAS G12C-driven tumours and reflects our commitment to bringing meaningful new treatment options to patients living with these cancers,” he added.
The designation is supported by preliminary findings from the ongoing Phase 1/2 LOXO-RAS-20001 open-label, multicentre study evaluating olomorasib in patients with advanced KRAS G12C-mutant solid tumours, including those with advanced pancreatic cancer who have received at least one prior systemic therapy.
Lilly is evaluating olomorasib across multiple clinical trials in patients with KRAS G12C-mutant cancers.
