Enfortumab vedotin (Padcev)

General information

Class/mechanism from the NCI Drug Dictionary: An antibody drug conjugate (ADC) containing a human monoclonal antibody AGS-22 targeting the cell adhesion molecule nectin-4 and conjugated to the cytotoxic agent monomethyl auristatin E (MMAE), via a proprietary enzyme-cleavable linker (AGS-22CE), with potential antineoplastic activity. The monoclonal antibody moiety of AGS-22CE selectively binds to nectin-4. After internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4 overexpressing tumor cells.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established

• Urothelial carcinoma

Patient drug information

• Enfortumab vedotin (Padcev) package insert
• Enfortumab vedotin (Padcev) patient drug information (Chemocare)
• Enfortumab vedotin (Padcev) patient drug information (UpToDate)

History of changes in FDA indication

• 2019-12-18: Granted accelerated approval for adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. (Based on EV-201)
• 2021-07-09: Regular approval for adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand (PD-L1) inhibitor and platinum-containing chemotherapy. (Based on EV-301)
• 2021-07-09: Regular approval for adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. (Based on EV-301)
• 2023-04-03: Granted accelerated approval with pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. (Based on EV-103)
• 2023-12-15: Approved in combination with pembrolizumab (Keytruda, Merck) for patients with locally advanced or metastatic urothelial cancer (la/mUC). (Based on EV-302)

History of changes in EMA indication

• 2022-04-13: Initial authorization as monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a programmed death receptor 1 or programmed death ligand 1 inhibitor.

History of changes in Health Canada indication

• 2021-10-29: Initial notice of compliance for the treatment of adult patients with unresectable locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor therapy.

History of changes in PMDA indication

• 2021-09-27: Newly indicated for the treatment of unresectable urothelial carcinoma that has progressed after cancer chemotherapy.

Also known as

• Code name: ASG-22CE
• Generic name: enfortumab vedotin-ejfv
• Brand name: Padcev