AUTHOR=Liu Jingrui , Zhang Hong , Zhu Xiaoxue , Chen Hong , Li Xiaojiao , Ding Yanhua 

TITLE=Phase I Trial to Evaluate the Tolerance, Pharmacokinetics and Efficacy of the Broad-Spectrum ErbB Family Inhibitor Larotinib Mesylate in Patients With Advanced Solid Tumors

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.636324

DOI=10.3389/fphar.2021.636324

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> The presented phase I, first-in-human study evaluated the tolerance, pharmacokinetics, and preliminary efficacy of larotinib mesylate in patients with advanced solid tumors.</p><p><bold>Methods:</bold> Cancer patients were assigned to receive larotinib mesylate at 50–400 mg dose levels until disease progression or intolerance. Dose-limiting toxicities were assessed during Cycles 0 and 1. Pharmacokinetic evaluations were performed after the first dose and at steady-state.</p><p><bold>Results:</bold> Twenty-five patients with solid tumors were enrolled in the dose-escalation study. No DLTs were observed. Acne-like rash (68.0%), diarrhea (48.0%), paronychia (48.0%), and anemia (48.0%) were the most reported treatment-related adverse events. No clear linear pharmacokinetic characteristic could be drawn, and obvious accumulation was observed. Two patients with non-small cell lung cancer experienced a partial response, and 15 patients had stable disease after treatment.</p><p><bold>Conclusion:</bold> Continuous oral administration of larotinib mesylate at 50–400 mg daily demonstrated a favorable safety profile, and anti-tumor activity was observed in patients with advanced solid tumors.</p>