Single-center phase 1-2 trial of first-line firmonertinib plus anlotinib for advanced non-small cell lung cancer with EGFR mutations

A phase 1-2 trial at the Chinese Academy of Medical Sciences & Peking Union Medical College (Beijing) evaluated the first-line oral combination of firmonertinib and anlotinib for locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations. A total of 36 patients were enrolled. Patients received firmonertinib once daily and anlotinib on days 1-14 in 21-day cycles. In the dose-exploration phase, 2 patients received anlotinib 8 mg, 3 patients received anlotinib 10 mg, and 3 patients received anlotinib 12 mg, all in combination with firmonertinib 80 mg. In the dose-expansion phase, 5 patients received anlotinib 10 mg and 23 received anlotinib 12 mg, in combination with firmonertinib 80 mg. The median duration of follow-up was 19.4 months. The objective response rate was 63.9% and the disease control rate was 100%, with a median duration of response of 23.0 months (95% CI 12.1-34.0) and median progression-free survival of 19.6 months (16.9-22.3). Grade ≥ 3 TRAEs occurred in 36.1%, dose reductions in 47.2%, and treatment discontinuation in 33.3%. The authors conclude that the first-line combination of firmonertinib and anlotinib demonstrated preliminary efficacy and manageable safety among patients with advanced NSCLC harboring EGFR mutations.