The US Food and Drug Administration (FDA) has granted accelerated approval to Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) for first-line treatment of adults with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-containing chemotherapy.

The approval was based on response rate and durability of response observed in the phase 1b/2 EV-103 trial ( Identifier: NCT03288545), which included patients with la/mUC who did not receive prior systemic therapy and were not eligible for cisplatin-containing chemotherapy.

In the dose-escalation cohort and cohort A of this trial, patients received enfortumab vedotin-ejfv with pembrolizumab. In cohort K, patients were randomly assigned to receive either the combination or enfortumab vedotin-ejfv alone. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR).

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Among 121 patients who received enfortumab vedotin-ejfv plus pembrolizumab, the ORR was 68%. The complete response rate was 12%, and the partial response rate was 55%. The median DOR for the dose-escalation cohort and cohort A was 22.1 months. The median DOR was not reached for cohort K.

The most common adverse reactions reported were increased glucose, increased aspartate aminotransferase, rash, decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased lymphocytes, fatigue, increased alanine aminotransferase, decreased sodium, increased lipase, decreased albumin, alopecia, decreased phosphate, decreased weight, diarrhea, pruritus, decreased appetite, nausea, dysgeusia, decreased potassium, decreased neutrophils, urinary tract infection, constipation, increased potassium, increased calcium, peripheral edema, dry eye, dizziness, arthralgia, and dry skin.  

Continued approval of this indication is contingent upon verification and description of clinical benefit from the ongoing phase 3 EV-302 trial ( Identifier: NCT04223856).


FDA grants accelerated approval for Padcev® (enfortumab vedotin-ejfv) with Keytruda® (pembrolizumab) for first-line treatment of locally advanced or metastatic urothelial cancer. News release. Astellas Pharma Inc. April 3, 2023. Accessed April 4, 2023.

FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. News release. US Food and Drug Administration. April 3, 2023. Accessed April 4, 2023.

Package insert. Astellas Pharma US, Inc.; 2023. Accessed April 4, 2023.

Package insert. Merck; 2023. Accessed April 4, 2023.

This article originally appeared on MPR