Lilly reports updated ESMO 2026 results for olomorasib in first-line KRAS G12C-mutant NSCLC, with response rates of 72.6% and 62% across two combinations.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company reported updated data on investigational olomorasib in previously untreated KRAS G12C-mutant non-small cell lung cancer (NSCLC) at the 2026 European Society for Medical Oncology (ESMO) Congress. Presented on October 25, the findings covered olomorasib combined with pembrolizumab, with or without platinum-based chemotherapy, using analyses from the Phase 1/2 LOXO-RAS-20001 study and the Phase 3 SUNRAY-01 programme.
Olomorasib Plus Pembrolizumab: Responses Remain Durable
The updated analysis included 43 patients from Part G of LOXO-RAS-20001 and 42 from the SUNRAY-01 dose-optimization cohorts. The safety population comprised 85 patients, of whom 84 were evaluable for efficacy. Patients received olomorasib 50 mg or 100 mg twice daily with pembrolizumab 200 mg intravenously every three weeks. Median follow-up was 20.7 months, with a data cutoff of March 5, 2026.
The confirmed investigator-assessed objective response rate (ORR) was 72.6% (61/84), increasing to 77.8% (42/54) among patients whose tumours expressed programmed death-ligand 1 (PD-L1) at 50% or higher. Median duration of response (DOR) and progression-free survival (PFS) had not been reached. The estimated 18-month PFS rate was 54.9% overall and 64.5% in the PD-L1-high subgroup.
These findings indicate sustained antitumour activity during follow-up, although the subgroup results do not establish PD-L1 expression as a predictive marker of greater benefit.
Safety Profile of the Pembrolizumab Combination
Treatment-related adverse events (TRAEs) occurred in 90.6% of patients (77/85). The most common Grade 3 or higher TRAEs were increased alanine aminotransferase (ALT; 15.3%), increased aspartate aminotransferase (AST; 12.9%) and diarrhoea (8.2%). Grade 4 ALT and AST events were also reported. TRAEs led to olomorasib dose reductions in 31.8% of patients and discontinuation of the treatment regimen in 11.8%. No Grade 5 TRAEs were reported.
Olomorasib Plus Chemoimmunotherapy: Efficacy Outcomes
A separate analysis evaluated olomorasib with pembrolizumab, pemetrexed and platinum chemotherapy (cisplatin or carboplatin). It included 37 patients from Cohort B9 of LOXO-RAS-20001 and 40 from the SUNRAY-01 safety lead-in, for 77 patients overall. Median follow-up was 18.7 months, and approximately 74% of patients had PD-L1 expression below 50%.
The confirmed investigator-assessed ORR was 62% (48/77). Median DOR was 14.5 months (95% confidence interval [CI], 8.5 months to not estimable), while median PFS was 11.6 months (95% CI, 9.5–21.5).
TRAEs occurred in 96.1% of patients (74/77). The most common Grade 3 or higher TRAEs were neutropenia (21%), anaemia (17%), increased ALT (12%) and thrombocytopenia (12%). TRAEs led to olomorasib dose reductions in 19.5% of patients and treatment-regimen discontinuation in 7.8%. No Grade 5 TRAEs were reported.
Regulatory Status and Phase 3 Development
Lilly reported that olomorasib plus pembrolizumab received US Food and Drug Administration (FDA) Breakthrough Therapy designation for first-line KRAS G12C-mutant NSCLC with PD-L1 expression of at least 50%. This designation supports expedited development and review but does not constitute marketing approval.
The global SUNRAY-01 programme includes randomized, placebo-controlled Phase 3 comparisons. Part A evaluates olomorasib plus pembrolizumab against pembrolizumab alone in patients with PD-L1 expression of at least 50%. Part B evaluates olomorasib plus chemoimmunotherapy against chemoimmunotherapy alone, regardless of PD-L1 expression, and has completed enrollment. Part C is designed to assess olomorasib plus pembrolizumab in patients with PD-L1 expression below 50%.
Lilly expects the first randomized Phase 3 data in first-line KRAS G12C-mutant NSCLC in the first half of 2027. Olomorasib remains investigational and is not approved by the FDA or any other regulatory authority for any use.
Clinical Interpretation
The updated analyses support continued evaluation of olomorasib with immunotherapy, with or without chemotherapy, in first-line KRAS G12C-mutant NSCLC. The pembrolizumab combination showed a confirmed ORR of 72.6%, with median DOR and PFS not reached after 20.7 months of median follow-up. The chemoimmunotherapy analysis reported a 62% ORR and median PFS of 11.6 months.
These results come from separate, non-randomized analyses and should not be interpreted as a head-to-head comparison. Differences in response rates and follow-up do not establish that either regimen is more effective, and the reported findings do not demonstrate an overall survival advantage. The randomized SUNRAY-01 results will be important to determine whether the observed activity translates into improved outcomes over established first-line regimens.
References
Eli Lilly and Company. New Data on Lilly’s Investigational Treatment Olomorasib at ESMO 2026 Show Durable First-Line Activity in KRAS G12C-Mutant Non-Small Cell Lung Cancer. October 25, 2026.
First-line Olomorasib + Pembrolizumab in KRAS G12C-Mutant NSCLC: Updated Results from LOXO-RAS-20001 and SUNRAY-01. ESMO Congress 2026 poster.
First-line Olomorasib + Chemoimmunotherapy in KRAS G12C-Mutant NSCLC: Updated Results from the LOXO-RAS-20001 and SUNRAY-01 Trials. ESMO Congress 2026 rapid oral presentation.
A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab with or Without Chemotherapy in Patients with Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer (SUNRAY-01), ClinicalTrials.gov ID NCT06119581
Study of LY3537982 in Cancer Patients with a Specific Genetic Mutation (KRAS G12C), ClinicalTrials.gov ID NCT04956640
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.