EMA accepts enfortumab vedotin application for urothelial carcinoma

March 26, 2021
Jason M. Broderick

The European Medicines Agency (EMA) has accepted a marketing authorization application (MAA) for enfortumab vedotin (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a PD-1/PD-L1 inhibitor, as well as platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.1

The MAA is supported by findings from the phase 3 EV-301 trial, in which the antibody-drug conjugate enfortumab vedotin reduced the risk of death by 30% versus chemotherapy in this setting.2,3

“In the European Union, it is estimated that 118,000 people are diagnosed with urothelial cancer each year, and 52,000 die as a result of the disease,” Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head, Astellas, stated in a press release. “People with advanced urothelial cancer face an urgent need for new treatment options, which is reflected in the CHMP’s decision to grant accelerated assessment. We will continue to work with the CHMP toward our goal of securing marketing authorization as soon as possible.”

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.

Baseline characteristics were balanced between the 2 arms. The median age was 68 years and more than three-fourths of patients were male. Only 14% of patients were from the United States, 60% had an ECOG performance status of 1, two-thirds had a Bellmunt risk score of 0 or 1, 31% had liver metastases, and 87% had 1 or 2 prior lines of therapy. In the enfortumab vedotin arm, 20% responded to prior immune checkpoint inhibition and 16% responded in the chemotherapy arm.

The median 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 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.


1. European Medicines Agency Accepts Marketing Authorization Application for Enfortumab Vedotin. Published online March 26, 2021. Accessed March 26, 2021. https://bwnews.pr/3lTCp3D.

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