Comprehensive first-in-human phase I/II study of FHND-9041 in patients with EGFR-mutated advanced non-small cell lung cancer

Abstract

<p><strong>Introduction: </strong>FHND-9041 is a novel third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI). This first-in-human study is a single-arm, multi-center, open-label, non-randomized phase Ⅰ/II trial that aims to evaluate the tolerability, safety, pharmacokinetics, and anti-tumor activity of FHND-9041 in patients with EGFR-mutated non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>The phase I study enrolled 87 patients with previously-treated EGFR T790M-positive NSCLC. The dose escalation study was conducted at doses of 40, 80, 120, and 180 mg/day, with an expansion of 36 and 39 patients in the 80 mg and 120 mg dose groups, respectively, to evaluate safety and pharmacokinetics. With 80 mg QD as the recommended phase II dose, the phase II study assessed the efficacy and safety of FHND-9041 as first-line treatment in 37 treatment-naive patients.</p><p><strong>Results: </strong>No dose-limiting toxicity was observed, and the maximum tolerated dose was not identified within the 40 - 180 mg dose range. Pharmacokinetic data indicated dose-proportional exposure up to 120 mg, with a plateau at 120 mg. The phase II study revealed an objective response rate of 62.2 % (23/37 evaluable patients) with a median progression-free survival of 15.5 months (95 % CI, 12.9 - 18.1). The most common adverse events were decreased white blood cell count (22.6 %) and diarrhea (21.8 %). Treatment-related grade 3/4 adverse events included decreased white blood cell count (11.3 %) and liver impairment (4.8 %).</p><p><strong>Conclusions: </strong>FHND-9041 exhibits favorable safety and efficacy profile, supporting its further clinical development for EGFR-mutated advanced NSCLC.</p>