Multinational phase 1b-2 trial of first-line fulzerasib plus cetuximab for KRAS-G12C mutated non-small cell lung cancer

The KRAS-G12C inhibitor fulzerasib has shown clinical activity in previously treated non-small cell lung cancer (NSCLC). Clinical studies have shown synergy between a KRAS-G12C inhibitor and an anti-EGFR antibody in colorectal cancer. The phase 1b-2 KROCUS trial, at 30 centers in Greece, Italy, and Spain, evaluated oral fulzerasib 600 mg twice daily plus intravenous cetuximab 500 mg/m² cetuximab every two weeks as first-line treatment for KRAS-G12C mutated NSCLC in adult patients with and ECOG performance status 0 oder 1. Primary endpoint was investigator-assessed objective response rate (ORR). A total of 47 patients received occurred in 6%. The authors conclude that in treatment-naïve KRAS-G12C mutated NSCLC, the combination of fulzerasib and cetuximab showed encouraging activity with a favorable safety profile.