Japanese subgroup analysis of EV‐301: An open‐label, randomized phase 3 study to evaluate enfortumab vedotin versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial carcinoma

BACKGROUND: Enfortumab vedotin (EV) is an antibody‐drug conjugate showing significant overall survival (OS) benefit versus chemotherapy for patients with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC) in EV‐301. This subgroup analysis was conducted to further analyze the efficacy and safety in a Japanese population. METHODS: In the open‐label, phase 3 EV‐301 trial, patients with la/mUC were randomized 1:1 to EV 1.25 mg/kg on Days 1, 8, and 15 for 28‐day cycles or investigator‐preselected standard chemotherapy (SC; docetaxel or paclitaxel for patients in Japan) on Day 1 of each 21‐day cycle. Primary endpoint was OS and secondary efficacy endpoints included progression‐free survival (PFS) and overall response rate (ORR). Safety/tolerability was also evaluated. RESULTS: As of the July 15, 2020 cut‐off date for the interim analysis, the Japanese subgroup included 86 patients (EV: n = 36; SC: n = 50). Median OS was 15.18 months for EV and 10.55 months for SC (HR: 0.437 [95% CI: 0.209, 0.914]). Median PFS was 6.47 months for EV and 5.39 months for SC (HR: 0.464 [95% CI: 0.258, 0.835]). Confirmed ORR was 34.4% for EV and 21.3% for SC. A higher proportion of patients receiving SC versus EV had treatment‐related adverse events (TRAEs; 97.9% vs. 91.7%, respectively), including grade ≥ 3 TRAEs (75.0% vs. 63.9%). CONCLUSIONS: This subgroup analysis confirmed that EV, with consistent efficacy and safety/tolerability in the EV‐301 Japanese subgroup and overall study population, represents an important treatment option for previously treated patients with la/mUC.