FDA Grants Breakthrough Status to Olomorasib in Pancreatic Cancer

The FDA has granted breakthrough therapy designation to olomorasib (LY3537982) as monotherapy for adult patients with advanced pancreatic cancer harboring a KRAS G12C mutation who have received at least 1 prior systemic therapy, as determined by an FDA-approved test.¹

Breakthrough therapy designation is intended to expedite the development and review of drugs for serious conditions when preliminary clinical evidence suggests the potential for substantial improvement over available therapy on a clinically significant end point. The designation provides for more intensive FDA guidance throughout development and may shorten the path to approval.

"Pancreatic cancer has historically been one of the most difficult-to-treat cancers and people whose tumors harbor a KRAS G12C mutation face limited options once their disease progresses," said Jacob Van Naarden, executive vice president,and president of Lilly Oncology, in a news release. "This [b]reakthrough [t]herapy designation reflects the early potential we're seeing with olomorasib in this setting and the critical need for new treatment options. With now [2] breakthrough therapy designations across pancreatic and lung cancers, olomorasib continues to demonstrate broad potential clinical evidence across KRAS G12C-driven tumors and reflects our commitment to bringing meaningful new treatment options to patients living with these cancers."

About Olomorasib

KRAS G12C mutations occur in an estimated 1% to 2% of patients with pancreatic cancer.¹ Despite the high prevalence of KRAS alterations across RAS-driven malignancies, no therapies are currently approved that specifically target KRAS G12C-mutant pancreatic cancer, leaving a gap for patients whose disease harbors this mutation. To meet this need, olomorasib was designed as an oral next-generation inhibitor designed to selectively target the KRAS G12C protein.

This marks the second breakthrough therapy designation for the agent; the first was granted in September 2025 for olomorasib in combination with pembrolizumab (Keytruda) as a first-line treatment for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and PD-L1 expression of 50% or higher, as determined by FDA-approved tests.

Clinical Development Programs

The decision is supported by preliminary findings from the ongoing, open-label, multicenter, phase 1/2 LOXO-RAS-20001 trial (NCT04956640), which is evaluating the safety, tolerability, and preliminary efficacy of olomorasib in patients with KRAS G12C–mutant advanced solid tumors, including those with advanced pancreatic cancer following at least 1 prior line of systemic therapy.² The study consists of a phase 1a dose-escalation portion of olomorasib monotherapy and a phase 1b dose-expansion and optimization portion evaluating the agent both as monotherapy and in combination with other treatments.

Beyond LOXO-RAS-20001, olomorasib is also being evaluated in the pivotal, registrational SUNRAY-01 global trial (NCT06119581), which is investigating the agent in combination with pembrolizumab (Keytruda), with or without chemotherapy, as first-line treatment for KRAS G12C–mutant advanced NSCLC, and in the SUNRAY-02 global trial (NCT06890598), which is evaluating olomorasib in combination with standard-of-care immunotherapy in patients with resected or unresectable KRAS G12C-mutant NSCLC.

REFERENCES

1. Lilly's olomorasib receives U.S. FDA's Breakthrough Therapy designation for the treatment of previously treated KRAS G12C-mutant advanced pancreatic cancer. News release. Eli Lilly and Company. August 3, 2026. Accessed August 3, 2026. https://tinyurl.com/3k4utsfn

2. Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C). ClinicalTrials.gov. Updated May 29, 2026. Accessed August 3, 2026. https://clinicaltrials.gov/study/NCT04956640