Biomarker Analyses in Patients With Advanced Solid Tumors Treated With the LAT1 Inhibitor JPH203
Naohiro Okano, Kiyomi Hana, Daisuke Naruge, Kirio Kawai, Takaaki Kobayashi, Fumio Nagashima, Hitoshi Endou, Junji Furuse
Abstract
BACKGROUND/AIM: Amino acids are among the most important nutrients for supplying energy and building protein blocks in cancers. L-type amino acid transporter (LAT) 1 is known to play a critical role in cancer growth. We have completed the first-in-human phase I study using the LAT1-specific inhibitor JPH203. PATIENTS AND METHODS: We evaluated plasma free amino acids (PFAAs), body mass index (BMI), and efficacy of JPH203 in patients enrolled in the phase I study. RESULTS: LAT1-substrate PFAAs and branched chain amino acids (BCAAs) were higher in patients with biliary tract cancer (BTC) than in those with other cancers. High inhibition of uptake of LAT1-substrate PFAAs was associated with survival. BMI of more than the median was associated with disease control and survival. BCAAs tended to be associated with BMI. CONCLUSION: BCAAs and BMI are useful predictors of the efficacy of JPH203, which shows promising activity against BTC.