A Phase I Study of Enfortumab Vedotin in Japanese Patients with Locally Advanced or Metastatic Urothelial Carcinoma - Expert Commentary

Enfortumab Vedotin (EV) is a novel antibody-drug conjugate targeting Nectin-4, which is overexpressed in urothelial cancer. A recent study published by Takahashi et al. in Investigational New Drugs studied EV in locally advanced/metastatic urothelial cancer in a phase I study (NCT03070990).1

The researchers included patients who were diagnosed with locally advanced or metastatic urothelial carcinoma and were cisplatin-ineligible or failed at least one chemotherapy treatment. Nine patients were randomly assigned to Arm A to receive EV at 1.0 mg/kg, and eight patients were assigned to Arm B to receive EV at 1.25 mg/kg on days 1, 8, and 15 of 28-day cycles.

The investigators found a dose-dependent increase in EV maximum concentration and area under the concentration-time curve on Day 7. Generally, EV was well-tolerated at both doses by patients in both arms. The most common adverse events related to EV were dysgeusia (n = 9) and alopecia (n = 9). In Arm A, 2/9 patients experienced EV-related adverse events (anemia and pyrexia n=1 each), and 2/8 in Arm B experienced three EV-related adverse events (bacterial pneumonia, erythematous rash, and hypertension). 10/17 patients experienced grade ≥ 3 adverse events.  In Arm A, 1/17 patients had a confirmed complete response, and 5/17 had confirmed partial responses. The objective response rate was 35.3%, and the disease control rate was 76.5%. The investigators concluded that EV was well-tolerated and showed promising antitumor activity in Japanese patients with locally advanced and metastatic urothelial cancer.

This study adds to the growing body of evidence supporting the efficacy and safety of antibody-drug conjugates in patients with advanced urothelial carcinoma.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. 1. Takahashi S, Uemura M, Kimura T, Kawasaki Y, Takamoto A, Yamaguchi A, Melhem-Bertrandt A, Gartner EM, Inoue T, Akazawa R, Kadokura T, Tanikawa T. A phase I study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma. Invest New Drugs. 2019 Aug 14. doi: 10.1007/s10637-019-00844-x.
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