On August 3, 2026, Eli Lilly and Company announced that the US Food and Drug Administration (FDA) had granted Breakthrough Therapy designation to olomorasib as monotherapy for adults with advanced pancreatic cancer who have received at least one prior systemic therapy and whose tumours harbour a KRAS G12C mutation, as determined by an FDA-approved test.
The designation is intended to expedite the development and review of therapies for serious conditions when preliminary clinical evidence indicates that a treatment may provide substantial improvement over available therapies on a clinically significant endpoint. It also provides more intensive FDA guidance during development and may accelerate the path toward regulatory approval.
What is Olomorasib?
Olomorasib, also known as LY3537982, is an investigational, oral, potent and highly selective next-generation inhibitor of the KRAS G12C protein. It was designed to target KRAS G12C-mutant cancers and has pharmacokinetic properties intended to support high predicted target occupancy and potency when administered alone or in combination with other treatments.
Lilly has described olomorasib as a highly potent covalent inhibitor of KRAS G12C. The agent has pharmacokinetic properties that allow for high predicted target occupancy and high potency when used as monotherapy or in combination with other treatments.
Olomorasib is being evaluated as monotherapy and in combination with other treatments across KRAS G12C-mutant advanced solid tumours. Its clinical development programme includes the phase 1/2 LOXO-RAS-20001 study, as well as studies combining olomorasib with pembrolizumab, chemotherapy or standard-of-care immunotherapy in different settings of KRAS G12C-mutant non-small cell lung cancer.
source: Eli Lilly and Company
Supporting Evidence From LOXO-RAS-20001
The Breakthrough Therapy designation was based on encouraging preliminary findings from LOXO-RAS-20001, an open-label, multicentre phase 1/2 study evaluating LY3537982 in patients with KRAS G12C-mutant advanced solid tumours. The study includes patients with advanced pancreatic cancer who have received at least one previous systemic therapy.
LOXO-RAS-20001, also identified as NCT04956640, is evaluating the safety, tolerability and preliminary efficacy of olomorasib. It includes a phase 1a dose-escalation component evaluating olomorasib monotherapy and a phase 1b dose-expansion and optimisation component evaluating the agent alone and in combination with other treatments. Detailed efficacy and safety results supporting the designation were not reported in the announcement.
KRAS G12C-Mutant Pancreatic Cancer
KRAS mutations are found in approximately 90% of pancreatic cancers, while the KRAS G12C variant occurs in approximately 1%–2% of patients with the disease.
According to Lilly, outcomes for patients with metastatic pancreatic cancer remain poor, with a five-year survival rate below 5%. The company also stated that growing evidence suggests that patients with KRAS G12C-mutant pancreatic cancer may have worse outcomes than patients without the mutation.
There are currently no approved therapies specifically targeting KRAS G12C-mutant pancreatic cancer.
Jacob Van Naarden, executive vice president and president of Lilly Oncology, said:
“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.”
“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 tumors and reflects our commitment to bringing meaningful new treatment options to patients living with these cancers.”
Olomorasib Development Programme
Olomorasib is being evaluated across several KRAS G12C-mutant cancers, including non-small cell lung cancer and other advanced solid tumours. The agent remains investigational.
Previous FDA Breakthrough Therapy Designation
The pancreatic cancer designation is the second FDA Breakthrough Therapy designation granted to olomorasib.
In September 2025, the FDA granted Breakthrough Therapy designation to olomorasib in combination with pembrolizumab for the first-line treatment of patients with unresectable or metastatic KRAS G12C-mutant non-small cell lung cancer whose tumours have PD-L1 expression of at least 50%, as determined by FDA-approved tests.
Breakthrough Therapy designation is intended to expedite the development and review of investigational therapies. It does not constitute FDA approval.
SUNRAY-01 and SUNRAY-02
LY3537982 is also being investigated in two global studies involving patients with KRAS G12C-mutant non-small cell lung cancer.
SUNRAY-01, identified as NCT06119581, is a pivotal, registrational study evaluating olomorasib in combination with pembrolizumab, with or without chemotherapy, as first-line treatment for advanced KRAS G12C-mutant non-small cell lung cancer.
SUNRAY-02, identified as NCT06890598, is evaluating olomorasib in combination with standard-of-care immunotherapy in patients with resected or unresectable KRAS G12C-mutant non-small cell lung cancer.
Find the full announcement on the official Eli Lilly and Company website.
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