Eli Lilly has reported encouraging clinical trial results for its experimental drug olomorasib in patients with advanced non-small cell lung cancer (NSCLC) carrying the KRAS G12C mutation, a form of the disease that remains difficult to treat.

 

Data presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid showed durable treatment activity when olomorasib was combined with the immunotherapy drug pembrolizumab, both with and without chemotherapy, in patients receiving first-line treatment.

 

In the combination that excluded chemotherapy, median progression-free survival (PFS) and median duration of response (DOR) had not been reached after a median follow-up of 20.7 months among 85 patients. The findings suggest that treatment responses may be sustained, although the study remains ongoing and the drug has not been approved for use.

 

In a separate analysis involving 77 patients treated with olomorasib alongside pembrolizumab and chemotherapy, the confirmed overall response rate was 62%. The median duration of response was 14.5 months, while median progression-free survival stood at 11.6 months after a median follow-up of 18.7 months.

 

The results strengthen the case for further testing olomorasib in a disease setting where treatment options remain limited and many patients never receive a second line of therapy.

 

Marcelo V. Negrao, Associate Professor of Thoracic and Head and Neck Medical Oncology at The University of Texas Anderson Cancer Center and presenting author of the study, said: "Responses lasting a median of more than a year in patients across all PD-L1 tumor expression levels - including many with low expression - is the type of progress we want to see in the first-line setting. 

 

"The data presented at ESMO support continued study of olomorasib with immunotherapy, with or without chemotherapy, to give patients the possibility of more options from the outset of their treatment journey, where we successfully utilize other genomically-targeted therapies in lung cancer."

 

KRAS G12C mutations occur in approximately 13% of people with NSCLC, the most common form of lung cancer. The mutation drives cancer growth and is associated with high-risk disease characteristics.

 

Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said: "KRAS G12C-mutant lung cancer has been notoriously difficult to treat, and for most patients, the disease is so aggressive that the first line is their only line, underscoring just how critical that first treatment choice is. These results deepen our conviction in the role olomorasib could play in combination with standard PD1-based backbone therapy, while potentially offering a tolerability profile that doesn't require prophylactic medications. 

 

"We recognize that the oncology community has been waiting for years for a targeted therapy regimen that can address first-line patients with G12C mutations, and we are hopeful that the pivotal Phase 3 data on olomorasib in combination with chemoimmunotherapy in the first half of next year will be a seminal moment for the field."

 

In the study of olomorasib plus pembrolizumab without chemotherapy, 64% of patients had PD-L1 expression levels of 50% or higher. Median progression-free survival and duration of response had not been reached in either the overall study population or this higher PD-L1 subgroup after 20.7 months of median follow-up.

 

However, the combination was not without adverse effects. The most common severe treatment-related adverse events were elevated alanine aminotransferase (ALT), reported in 15.3% of patients; elevated aspartate aminotransferase (AST), in 12.9%; and diarrhoea, in 8.2%.

 

In the chemotherapy-containing combination, most patients (74%) had PD-L1 expression below 50%. The most common severe treatment-related adverse events were neutropenia (21%), anaemia (17%), elevated ALT (12%) and thrombocytopenia (12%).

 

Dose reductions of olomorasib were required in 19.5% of patients, and 7.8% discontinued the treatment regimen because of treatment-related adverse events. No treatment-related deaths occurred in this group either.

 

Lilly said the safety profiles were consistent with previous reports and the known profiles of the medicines used in the combinations. Neither regimen required protocol-mandated prophylactic medication for olomorasib.