Biomarker Analyses in Patients With Advanced Solid Tumors Treated With the LAT1 Inhibitor JPH203

In Vivo. 2020 Sep-Oct;34(5):2595-2606. doi: 10.21873/invivo.12077.

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.

Keywords: JPH203; L-type amino acid transporter; amino acids; biliary tract cancer; body mass index.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Benzoxazoles
  • Biomarkers
  • Humans
  • Large Neutral Amino Acid-Transporter 1* / genetics
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Tyrosine / analogs & derivatives

Substances

  • 2-amino-3-(4-((5-amino-2-phenylbenzo(d)oxazol-7-yl)methoxy)-3,5-dichlorophenyl)propanoic acid
  • Benzoxazoles
  • Biomarkers
  • Large Neutral Amino Acid-Transporter 1
  • Tyrosine