A phase I study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma

Shunji Takahashi, Motohide Uemura, Tomokazu Kimura, Yoshihide Kawasaki, Atsushi Takamoto, Akito Yamaguchi, Amal Melhem-Bertrandt, Elaina M. Gartner, Takashi Inoue, Rio Akazawa, Takeshi Kadokura, Toshiki Tanikawa

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4 Citations (Scopus)

Abstract

Locally advanced or metastatic urothelial cancer is an aggressive form of cancer with high recurrence rates and low survival. Nectin-4 is a cell adhesion molecule commonly expressed in several tumors, including high expression in urothelial cancer. Enfortumab vedotin is an antibody–drug conjugate composed of an anti-Nectin-4 humanized monoclonal antibody linked to the microtubule disrupting agent, monomethyl auristatin E. In this phase I study (NCT03070990), Japanese patients with locally advanced/metastatic urothelial cancer treated with prior chemotherapy, or ineligible for cisplatin, were randomized 1:1 to receive 1.0 mg/kg (Arm A) or 1.25 mg/kg (Arm B) enfortumab vedotin on Days 1, 8, and 15 of each 28-day cycle. Assessing the pharmacokinetic and safety/tolerability profiles of enfortumab vedotin were primary objectives; investigator-assessed antitumor activity (RECIST v1.1) was a secondary objective. Seventeen patients (n = 9, Arm A; n = 8, Arm B) received treatment. Pharmacokinetic data suggest a dose-dependent increase in enfortumab vedotin maximum concentration and area under the concentration–time curve at Day 7. Enfortumab vedotin was well tolerated across both doses. Dysgeusia and alopecia (n = 9 each) were the most common treatment-related adverse events. Regardless of attribution, grade ≥ 3 adverse events occurring in ≥2 patients were anemia and hypertension (n = 2 each). One patient achieved a confirmed complete response (Arm A) and five achieved confirmed partial responses (n = 3, Arm A; n = 2, Arm B). Objective response and disease control rates were 35.3% and 76.5%, respectively. In Japanese patients with locally advanced/metastatic urothelial cancer, enfortumab vedotin is well tolerated with preliminary antitumor activity and a pharmacokinetic profile consistent with prior reports.

Original languageEnglish
Pages (from-to)1056-1066
Number of pages11
JournalInvestigational New Drugs
Volume38
Issue number4
DOIs
Publication statusPublished - 2020 Aug 1

Keywords

  • Immunoconjugates
  • Japan
  • Nectins
  • Neoplasms
  • Urothelium

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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    Takahashi, S., Uemura, M., Kimura, T., Kawasaki, Y., Takamoto, A., Yamaguchi, A., Melhem-Bertrandt, A., Gartner, E. M., Inoue, T., Akazawa, R., Kadokura, T., & Tanikawa, T. (2020). A phase I study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma. Investigational New Drugs, 38(4), 1056-1066. https://doi.org/10.1007/s10637-019-00844-x