Indianapolis, Indiana, U.S., October 25, 2026
Eli Lilly and Company announced updated clinical findings for olomorasib, its investigational next-generation KRAS G12C inhibitor, in patients receiving first-line treatment for advanced KRAS G12C-mutated non-small cell lung cancer (NSCLC). The data, presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, evaluated olomorasib in combination with pembrolizumab, both with and without chemotherapy. In the chemotherapy-free analysis, responses remained durable after a median follow-up of 20.7 months, while median progression-free survival and duration of response had not yet been reached. In a separate analysis combining olomorasib with pembrolizumab, pemetrexed and platinum chemotherapy, the confirmed objective response rate was 62%, with a median duration of response of 14.5 months. These findings support continued investigation of targeted KRAS inhibition alongside standard immunotherapy, although olomorasib remains investigational and requires further confirmation in randomized Phase 3 trials.
Olomorasib Combination Shows Durable First-Line Activity
Updated results for olomorasib plus pembrolizumab without chemotherapy included 85 patients from the Phase 1/2 LOXO-RAS-20001 study and the safety lead-in portion of the Phase 3 SUNRAY-01 study. After a median follow-up of 20.7 months, median progression-free survival and median duration of response had not been reached in the overall population. The majority of participants, 64%, had PD-L1 expression of at least 50%. Among the overall population, the estimated progression-free survival rate at 18 months was 55%, increasing to 65% among patients with PD-L1 expression of at least 50%. These findings suggest sustained clinical activity across PD-L1 expression levels, including in patients who may be candidates for immunotherapy without chemotherapy. The safety profile was consistent with earlier reports and the known profiles of the medicines. The most common Grade 3 or higher treatment-related adverse events were increased alanine aminotransferase (15.3%), increased aspartate aminotransferase (12.9%) and diarrhoea (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.
Chemoimmunotherapy Analysis Reports 62% Response Rate
A separate updated analysis evaluated olomorasib combined with pembrolizumab, pemetrexed and platinum chemotherapy in 77 patients receiving first-line treatment for advanced KRAS G12C-mutated NSCLC. Median follow-up was 18.7 months, and 74% of participants had PD-L1 expression below 50%. Investigators reported a confirmed objective response rate of 62%, with 48 of 77 patients responding to treatment. Median duration of response was 14.5 months, while median progression-free survival reached 11.6 months. The most common Grade 3 or higher treatment-related adverse events included neutropenia (21%), anaemia (17%), increased alanine aminotransferase (12%) and thrombocytopenia (12%). Treatment-related adverse events resulted in olomorasib dose reductions in 19.5% of patients and discontinuation of the treatment regimen in 7.8%. No Grade 5 treatment-related adverse events occurred. Because this was an updated single-arm analysis, the results do not establish superiority over standard treatment. Randomized studies will be needed to determine the combination’s comparative efficacy and safety.
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Lilly Advances Phase 3 SUNRAY-01 Clinical Programme
Olomorasib is an oral, selective KRAS G12C inhibitor designed to bind the mutated KRAS protein and lock it in an inactive state, interrupting signals that drive cancer growth. KRAS G12C mutations occur in approximately 13% of patients with NSCLC, creating a defined population for targeted treatment research. Lilly is investigating whether olomorasib can be combined with PD-1 immunotherapy, with or without chemotherapy, to improve first-line treatment options. The global Phase 3 SUNRAY-01 programme includes randomized comparisons of olomorasib-based regimens against placebo-based control regimens alongside standard treatment. One study evaluates olomorasib plus pembrolizumab in patients with PD-L1 expression of at least 50%, while another evaluates olomorasib plus chemoimmunotherapy across PD-L1 expression levels. Lilly expects the first randomized Phase 3 data from SUNRAY-01 in the first half of 2027. The company is also studying olomorasib in earlier-stage NSCLC. Olomorasib is not approved by the U.S. Food and Drug Administration or any other regulatory authority. The current findings are encouraging clinical signals, but the ongoing trials will be essential to determine whether the treatment can deliver a meaningful benefit for patients.
Source: Eli Lilly press release
