Enfortumab vedotin-ejfv for the treatment of advanced urothelial carcinoma

ABSTRACT

Introduction

Metastatic urothelial carcinoma is an aggressive malignancy with a poor prognosis. Research in recent years has led to the approval of new treatments that offer improved survival for patients. Enfortumab vedotin-ejfv is a first-in-class monoclonal antibody drug conjugate that binds Nectin-4, a protein expressed on bladder cancer cells, and delivers the tubulin toxin, monomethyl auristatin E, into the cell causing cell death. Enfortumab vedotin-ejfv has changed the standard of care treatment in urothelial carcinoma with a high response and disease-control rate, acceptable toxicity profile and improved overall survival for patients who previously had limited options after failure of chemotherapy and/or immunotherapy.

Areas covered

We review the pharmacology, clinical efficacy, safety, and tolerability of enfortumab vedotin.

Expert opinion

Enfortumab vedotin-ejfv has shown promising efficacy and safety in pretreated patients with advanced urothelial carcinoma. It is currently being evaluated in clinical trials in earlier lines of treatment and in combination therapy.

KEYWORDS:

• AGS-22C3
• antibody drug conjugate
• Enfortumab Vedotin
• EV
• MMAE
• Nectin-4

Article highlights

• Urothelial carcinoma is a common malignancy that has a poor prognosis in advanced disease

• Enfortumab vedotin is a novel antibody drug conjugate that binds Nectin-4, a protein highly expressed on urothelial carcinoma cells and delivers monomethyl auristatin E, a tubulin toxin, directly to cells

• Enfortumab vedotin has been studied in phase I-III clinical trials and has improved outcomes coupled with acceptable tolerability for pretreated patients with advanced urothelial carcinoma

• Early results in the investigation of combination enfortumab vedotin and pembrolizumab therapy have shown promising efficacy and durability.

• Enfortumab vedotin is currently being investigated as a treatment earlier in the disease course and in combination therapy

Declaration of interest

G Sonpavde has served on the Advisory Board for; BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Immunomedics/Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals; has received institutional research support from: Sanofi, Astrazeneca, Immunomedics/Gilead, QED, Predicine, BMS; has served on the steering committee of studies for: BMS, Bavarian Nordic, Seattle Genetics, QED, G1 Therapeutics (all unpaid), and Astrazeneca, EMD Serono, Debiopharm (paid); has served on the data safety monitoring committee for: Mereo; has received travel costs from: BMS, Astrazeneca; has received writing/editor fees from: Uptodate, Editor of Elsevier Practice Update Bladder Cancer Center of Excellence; and has received speaking fees from: Physicians Education Resource (PER), Onclive, Research to Practice, Medscape, Cancer Network, Masters Lecture Series.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.