Lilly's olomorasib shows durable first-line activity in KRAS G12C NSCLC

Efficacy data

Updated results presented at ESMO 2026 show durable first-line activity for olomorasib combined with standard PD‑1–based therapy. In a cohort of 85 patients treated with olomorasib plus pembrolizumab, median progression-free survival and median duration of response were not reached after a median follow-up of 20.7 months, with durable responses across PD‑L1 expression levels (64% had PD‑L1 ≥50%). In a separate cohort of 77 patients receiving olomorasib with pembrolizumab, pemetrexed and platinum chemotherapy, investigator-assessed confirmed ORR was 62% (48/77), median DOR was 14.5 months (95% CI, 8.5–NE) and median PFS was 11.6 months (95% CI, 9.5–21.5) after a median 18.7 months follow-up.

Safety and tolerability

Safety profiles were consistent with prior reports and known profiles of the backbone therapies. In the pembrolizumab-only cohort the most common Grade ≥3 treatment-related adverse events were increased ALT (15.3%), increased AST (12.9%) and diarrhea (8.2%); olomorasib dose reductions occurred in 31.8% and regimen discontinuation in 11.8%. In the chemoimmunotherapy cohort the most common Grade ≥3 TRAEs were neutropenia (21%), anemia (17%), increased ALT (12%) and thrombocytopenia (12%); dose reductions occurred in 19.5% and discontinuations in 7.8%. No Grade 5 TRAEs were reported and the protocol did not require prophylactic medications for olomorasib.

Trials and next steps

The data support the ongoing global Phase 3 SUNRAY‑01 master protocol (Parts A–C), which randomizes olomorasib plus pembrolizumab or plus chemoimmunotherapy versus placebo arms across PD‑L1 subgroups; Part B has completed enrollment. Lilly expects first randomized Phase 3 data from SUNRAY‑01 in first-line KRAS G12C NSCLC in the first half of 2027. The programme targets an unmet first-line need for patients with KRAS G12C–mutant NSCLC, a mutation present in about 13% of NSCLC cases where many patients do not reach second-line therapy.