Enfortumab vedotin nears bladder cancer approval in Japan

The Japanese Ministry of Health, Labour, and Welfare has granted priority review to a new drug application (NDA) for enfortumab vedotin for use in patients with locally advanced or metastatic urothelial carcinoma after progression on anticancer therapy, according to Astellas Pharma.1

Updated 9/27/21: Enfortumab vedotin approved in Japan for bladder cancer

The NDA is supported by data from the phase 3 EV-301 trial and the phase 2 EV-201 trial. Specifically in EV-301, the antibody-drug conjugate reduced the risk of death by 30% versus chemotherapy in patients with heavily pretreated locally advanced or metastatic urothelial carcinoma.2,3

"The decision by the Ministry of Health, Labour and Welfare to evaluate enfortumab vedotin under priority review reflects the urgent need for new medicines to treat advanced urothelial cancer in Japan, where an estimated 9,500 people die from urothelial cancer each year," stated Andrew Krivoshik, MD, PhD, senior vice president and Oncology Therapeutic Area Head, Astellas, which codevelops enfortumab vedotin with Seagen.

The open-label, randomized EV-301 trial (NCT03474107) included 608 patients with histologically or cytologically confirmed urothelial cancer, including patients with squamous differentiation or mixed cell types, were enrolled in the study and randomized 1:1 with stratification to either the enfortumab vedotin (n = 301) arm or the chemotherapy arm (n = 307).

Eligible patients had radiographic progression or relapsed during or after immune checkpoint inhibition for the treatment of advanced urothelial cancer and had received prior platinum-containing chemotherapy; patients also had an ECOG performance status of 0 or 1. Stratification variables included ECOG performance status (0 or 1), region of the world, and the presence or absence of liver metastasis.

The median overall survival (OS) with enfortumab vedotin was 12.88 months versus 8.97 months with chemotherapy, which translated to a 30% reduction in the risk of death (HR, 0.70; = .00142). Subgroup analyses for OS favored the enfortumab vedotin arm for all groups excepts female patients (HR, 1.17).

Median progression-free survival (PFS) with enfortumab vedotin was 5.55 months versus 3.71 months with chemotherapy (HR, 0.62; <.00001).

Confirmed ORR in the enfortumab vedotin arm was 40.6%, which included CRs in 4.9%, and the disease control rate (DCR) was 71.9%. In the chemotherapy arm, the ORR was 17.9% with CRs in 2.7%, and a DCR of 53.4% (< .001).

Treatment-related adverse event (TRAE) rates were similar between the 2 arms, with any-TRAE rates of 94% in the investigational arm and 92% in the control arm, and grade ≥3 TRAE rates of 51% and 50%, respectively. Serious TRAEs were reported in 23% of patients in each arm and TRAEs led to treatment discontinuation in 14% of patients in the enfortumab vedotin arm and 11% in the chemotherapy arm.

The single-arm, phase 2 EV-201 trial examined enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2).

Data for cohort 1 of the trial (n = 128) showed that the antibody-drug conjugate elicited an ORR of 44%, which included a 12% CR rate, and a 32% partial response rate.

The results for cohort 2 included 89 patients.4 The median time to response was 1.81 months with some patients who have durable responses that extend beyond a year or more. Median DOR was 10.9 months. At a median follow-up of 13.4 months, the median PFS was 5.8 months and median OS was 14.7 months.


1. Japan's Ministry of Health, Labour and Welfare Grants Priority Review for Enfortumab Vedotin New Drug Application. Published online May 13, 2021. Accessed May 14, 2021. https://prn.to/3hnRkTv.

2. Powles T, Rosenberg JE, Sonpavde G, et al. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2021;39(suppl 6):393. doi:10.1200/JCO.2021.39.6_suppl.393

3. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. Published online February 12, 2021. N Engl J Med. doi:10.1056/NEJMoa2035807

4. Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. J Clin Oncol. 2021;39(suppl 6).394. doi: 10.1200/JCO.2021.39.6_suppl.394