Multicenter phase 1b-2 trial expansion cohort of first-line ifebemtinib plus garsorasib for KRAS-G12C-mutated non-small cell lung cancer

The selective oral FAK inhibitor ifebemtinib has shown preclinical synergistic activity with KRAS^G12C inhibitors. Garsorasib is a novel KRAS^G12C inhibitor approved in China for patients with KRAS^G12C-mutated non-small cell lung cancer (NSCLC). A phase 1b-2 trial at eight centers in China evaluated the first-line combination of ifebemtinib and garsorasib in KRAS^G12C-mutated solid tumors. Results of the NSCLC expansion cohort have now been published. Eligible patients were adults with locally advanced or metastatic KRAS^G12C-mutated NSCLC, who were treatment-naïve and had an ECOG status of 0 or 1. The primary endpoint was objective response rate (ORR) as assessed by local investigators. Among 33 patients receiving at least one dose of ifebemtinib plus garsorasib, the ORR was 82% (95% CI 64.5-93.0). All patients reported treatment-emergent adverse events, with 11 patients (33%) experiencing grade 3 or 4 events, of which eight (24%) were related to study drugs. Serious adverse events occurred in nine patients (27%). No treatment-related deaths were reported. The authors conclude that the dual-oral chemotherapy-free regimen of ifebemtinib plus garsorasib had encouraging efficacy and manageable safety as first-line treatment for locally advanced or metastatic KRAS^G12C-mutated NSCLC.