First-in-human phaseIstudy of JPH203 in patients with advanced solid tumors.

419Background: Uptake of amino acids is essential for cancer growth. L-type amino acid transporter-1 (LAT-1) is overexpressed in various cancers, and uptake of LAT-1 substrate amino acids is known to have a critical role in cancer growth. JPH203 is a novel, selective, LAT-1 inhibitor. A first-in-human phase I study of JPH203 was designed to determine the safety, maximum-tolerated dose (MTD) and recommended dose. This study included evaluation of the anti-tumor effect, pharmacokinetics, and pharmacodynamics of JPH203 and analyzed plasma free amino acids. Methods: JPH203 was administered intravenously for 7 days followed by 21 days’ rest at planned doses ranging from 12 to 110 mg/m2 in patients with advanced solid tumors refractory to standard therapy. Before starting this schedule, we confirmed safety of a single dose of JPH203. Dose-limiting toxicity was evaluated during the first cycle, using a 3+3 design. Results: 17 patients were enrolled from January 2015 to August 2016. One patient was discontinued a...