FDA grants breakthrough therapy designation to Lilly’s olomorasib

The designation is specifically for patients whose tumours demonstrate a KRAS G12C mutation confirmed by an FDA-approved test and covers olomorasib administered as a monotherapy.

Olomorasib (LY3537982) is an investigational inhibitor targeting the KRAS G12C protein and belongs to a class of next-generation therapies under study for various solid tumours.

This marks the second breakthrough therapy designation the experimental drug has received from the US regulator.

In September 2025, the FDA designated olomorasib in combination with Keytruda (pembrolizumab) for the first-line treatment of metastatic or locally advanced non-small cell lung cancer (NSCLC) in patients testing positive for KRAS G12C mutations and a PD-L1 expression of 50% or higher.

Both designations require molecular confirmation through FDA-recognised testing methods.

Breakthrough therapy status is granted to drug candidates that show initial clinical evidence of significant benefits over existing therapies in the treatment of serious conditions.

The FDA’s latest decision for olomorasib was based on preliminary findings from the open-label, multicentre, Phase I/II LOXO-RAS-20001 trial.

This study is assessing safety, tolerability, and early signs of efficacy in people with KRAS G12C-mutant advanced solid tumours, including advanced pancreatic cancers previously exposed to systemic treatment.

Lilly executive vice-president and oncology president Jacob Van Naarden  said: “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. 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.”

LOXO-RAS-20001 includes both a Phase Ia dose escalation stage for monotherapy and a Phase Ib expansion phase looking at olomorasib alone and in combination with other treatments.

According to Lilly, KRAS mutations account for the majority of RAS-associated cancers in humans and appear in 90% of pancreatic cancers, with the G12C subtype estimated in 1% to 2% of patients with this disease.

Recently, Lilly expanded its partnership with Resilience by investing in Ohio-based pharmaceutical manufacturing to boost US production of critical medicines.