Enfortumab vedotin data published as FDA weighs expanded bladder cancer approval


Data from the phase 2 EV-201 trial supporting a potential expanded FDA approval of enfortumab vedotin (Padcev) in bladder cancer have been published in the Lancet Oncology.1

Specifically, the published data are for cohort 2 of the EV-201 study, in which the antibody-drug conjugate (ADC) enfortumab vedotin was administered to cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior anti–PD-1/PD-L1 therapy. The confirmed objective response rate (ORR) in these patients was 52%.

Based on the results from this cohort, the FDA is currently reviewing a supplemental biologics license applications (sBLA) seeking to expand the approval of the ADC for use in this patient population.

“These patients have few treatment options, and enfortumab vedotin could be a promising new therapy for a patient population with a high unmet need,” lead study author Evan Y. Yu, MD, a professor in the Department of Medicine, Division of Oncology, University of Washington and Fred Hutchinson Cancer Research Center, and coauthors wrote in their study conclusion.

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) supported the accelerated approval of enfortumab vedotin. In these patients, 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 data from 89 patients. Baseline characteristics showed that patients were a median age of 75, male (74%), and 15% were obese. Two-thirds (67%) of patients exhibited a moderate decrease in kidney function. Looking at the primary site of tumor, 43% had a tumor in the upper tract.

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.

In terms of safety, any grade overall TRAEs occurred in 97% of patients and grade 3 or higher TRAEs occurred in 55% of patients. TRAEs led to discontinuations in 16% of patients, and peripheral sensory neuropathy was the most common in 4%. There were 4 deaths that were considered to be treatment related by the investigator and these were a result of acute kidney injury, metabolic acidosis, multiple organ dysfunction syndrome, and pneumonitis.

The FDA is also currently reviewing a separate sBLA that is intended to convert the drug’s accelerated approval into a full approval. This sBLA is based on results from the confirmatory phase 3 EV-301 trial, which were shared during the 2021 Genitourinary Cancers Symposium.2,3 In the study, enfortumab vedotin reduced the risk of death by 30% versus chemotherapy in patients with heavily pretreated locally advanced or metastatic urothelial carcinoma.

The FDA is scheduled to make a decision on the 2 sBLAs on or before August 17, 2021.


1. Yu EY, Petrylak DP, O'Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial [published online ahead of print May 12, 2021]. Lancet Oncol. doi: 10.1016/S1470-2045(21)00094-2

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

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