Olomorasib shows durable first-line activity in KRAS G12C-mutant lung cancer
Posted on October 27, 2026
Eli Lilly has reported new clinical data showing durable activity with its investigational KRAS G12C inhibitor olomorasib in combination with standard first-line immunotherapy, with or without chemotherapy, in patients with advanced KRAS G12C-mutant non-small cell lung cancer.
The findings were presented at the 2026 European Society for Medical Oncology Congress and included updated results from the Phase I/II LOXO-RAS-20001 study and the safety lead-in portion of the Phase III SUNRAY-01 programme.
Olomorasib is an investigational next-generation oral KRAS G12C inhibitor designed to bind the mutated KRAS protein and maintain it in an inactive state.
In one analysis, olomorasib was combined with pembrolizumab without chemotherapy in 85 previously untreated patients with KRAS G12C-mutant non-small cell lung cancer.
After a median follow-up of 20.7 months, median progression-free survival had not yet been reached.
Median duration of response had also not been reached.
Lilly said durable activity was observed across PD-L1 expression levels.
Around 64% of patients in the analysis had PD-L1 expression of 50% or higher, and median progression-free survival and duration of response had not been reached in this subgroup either.
The safety profile of olomorasib plus pembrolizumab was consistent with previous findings and the established profile of the individual treatments.
The most common Grade 3 or higher treatment-related adverse events were increased alanine aminotransferase levels in 15.3% of patients, increased aspartate aminotransferase levels in 12.9% and diarrhoea in 8.2%.
Treatment-related adverse events led to olomorasib dose reductions in 31.8% of patients and discontinuation of the treatment regimen in 11.8%.
No Grade 5 treatment-related adverse events were reported.
A separate analysis evaluated olomorasib in combination with pembrolizumab, pemetrexed and platinum chemotherapy in 77 patients receiving first-line treatment.
At a median follow-up of 18.7 months, the confirmed investigator-assessed overall response rate was 62%, representing 48 of 77 patients.
Median duration of response reached 14.5 months, while median progression-free survival was 11.6 months.
Most patients in this analysis, or 74%, had PD-L1 expression below 50%.
The most common Grade 3 or higher treatment-related adverse events with the chemoimmunotherapy combination were neutropenia in 21% of patients, anaemia in 17%, increased alanine aminotransferase levels in 12% and thrombocytopenia in 12%.
Treatment-related adverse events resulted in olomorasib dose reductions in 19.5% of patients and discontinuation of the regimen in 7.8%.
No Grade 5 treatment-related adverse events were reported in this analysis.
Marcelo V. Negrao, MD, Associate Professor of Thoracic and Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, said the durability of responses across PD-L1 expression groups supports further investigation of olomorasib in combination with immunotherapy.
KRAS G12C mutations are found in approximately 13% of patients with non-small cell lung cancer.
There are currently no approved targeted therapies specifically for the first-line treatment of KRAS G12C-mutant disease, with immunotherapy alone or combined with chemotherapy remaining the standard approach.
Lilly said the new findings support continued development through the Phase III SUNRAY-01 programme.
Part A of the study is evaluating olomorasib plus pembrolizumab against placebo plus pembrolizumab in patients with PD-L1 expression of at least 50%.
Part B is assessing olomorasib plus chemoimmunotherapy against placebo plus chemoimmunotherapy regardless of PD-L1 expression and has completed enrolment.
Part C is designed to evaluate olomorasib plus pembrolizumab in patients with PD-L1 expression below 50%.
Lilly expects the first randomised Phase III results from SUNRAY-01 in the first half of 2027.
Related Topics and Keywords
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