Firmonertinib plus anlotinib shows preliminary efficacy in advanced EGFR-mutant NSCLC.

BACKGROUND: This single-arm, phase I/II trial aimed to evaluate the efficacy and safety of firmonertinib plus anlotinib as first-line treatment for patients with non small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. METHODS: We enrolled patients aged 18 years or older and had locally advanced or metastatic NSCLC harboring EGFR sensitive mutation. Patients were treated with oral firmonertinib 80 mg once daily combined with oral anlotinib (days 1-14 in 21-day cycle). The primary endpoint was objective response rate (ORR). RESULTS: Between March, 19th, 2022 and July, 27th, 2023, 36 patients were enrolled. In dose-exploration phase, 2 patients were treated with anlotinib 8 mg, 3 were treated with anlotinib 10 mg and 3 were treated with anlotinib 12 mg combined with firmonertinib 80 mg. In dose-expansion phase, 5 were treated with 10 mg anlotinib and 23 were treated with anlotinib 12 mg combined with firmonertinib 80 mg. The median follow-up time was 19.4 months. ORR was 63.9% and disease control rate (DCR) was 100.0%. Median progression free survival (PFS) was 19.6 months (95% CI 16.9-22.3). Median duration of response (DoR) was 23.0 months (95% CI 12.1-34.0). Concurrent pathogenic TP53 mutation was an independent prognostic factor (HR 2.38, 95% CI 0.90-6.30, P = .07). Diarrhea and hypertension were the most common TRAEs. ≥Grade 3 TRAEs occured in 36.1% patients. 47.2% patients experienced dose reduction and 33.3% patients experienced treatment discontinuation. CONCLUSION: Firmonertinib plus anlotinib demonstrated preliminary efficacy and manageable safety as first-line treatment among patients with NSCLC harboring EGFR mutations.