Olomorasib (KRAS G12C inhibitor) + pembrolizumab maintains ~72–77% ORR despite 1 prior SOC cycle in 1L NSCLC

Olomorasib is an oral covalent KRAS G12C inhibitor combined with pembrolizumab (PD-1) with or without platinum/pemetrexed chemotherapy in 1L advanced KRAS G12C–mutant NSCLC (PD-L1 0–100%, ECOG 0–1) in LOXO-RAS-20001 and the SUNRAY-01 safety lead-in (NCT04956640; NCT06119581; data cutoff June 6, 2025). In the doublet, ORR was 76.9% with 1 prior SOC cycle vs 71.8% with no prior SOC (n=13 vs n=72), with Grade 3+ TRAEs 30.8% vs 41.7% and Grade 3+ hepatic events 15.4% vs 22.2%; in the quad, ORR was 73.9% vs 55.6% (n=23 vs n=54) with Grade 3+ TRAEs 26.1% vs 59.3% and Grade 3+ neutropenia 4.3% vs 16.7% (discontinuation 0% vs 11.1%). While cross-trial comparisons are imperfect, these ORRs sit well above typical 1L pembrolizumab + platinum/pemetrexed response rates in metastatic nonsquamous NSCLC (KEYNOTE-189 ORR ~48% range) and suggest the “1 bridging cycle” doesn’t obviously dilute efficacy signals during molecular-testing turnaround.