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

Journal: In vivo (Athens, Greece) 2021;34(5):2595-2606

PMID: 32871789

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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.

Address: Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan [email protected].; J-Pharma Co., Ltd., Kanagawa, Japan.; Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

DOI: 10.21873/invivo.12077