Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to monomethyl auristatin E for metastatic urothelial Carcinoma

ABSTRACT

Introduction: The conventional management of most patients with metastatic urothelial carcinoma (UC) is platinum-based chemotherapy followed by immunotherapy. Erdafitinib is an option in post-platinum patients with activating mutations in fibroblast growth factor receptor (FGFR)-3 and −2. Salvage therapy with taxanes or vinflunine has demonstrated minimal efficacy. Enfortumab Vedotin (EV), a monoclonal antibody-drug conjugate (ADC) targeting nectin-4 is under investigation in patients with advanced UC.

Areas covered: This review describes the epidemiology and unmet needs of patients with metastatic UC and is focused specifically on heavily treated patients. We explore the rationale for targeting nectin 4 and the clinical development of EV; efficacy and safety data from the completed phase I and II studies are examined. Ongoing trials to definitively assess clinical outcomes in comparison to current therapy and trials exploring EV in combination are also highlighted.

Expert opinion: There is an unmet need for new therapies in most patients with advanced UC and who progress after platinum and immunotherapy. EV has shown promising efficacy and safety in this population in phase 1 and 2 trials including those with poor prognostic factors such as liver metastases. Ongoing trials exploring this agent in combination will continue to advance the treatment of UC.

KEYWORDS:

• Antibody-drug conjugates
• Enfortumab vedotin
• metastatic Urothelial carcinoma
• Nectin 4

Declaration of interest

BA McGregor has received consulting/advisory fees from Astellas/Seattle Genetics, AstraZeneca, Nektar, Exelixis, Pfizer, Bayer, Genentech, Janssen, EMD Serono and Decibel Therapeutics; Institutional Research Support from Bristol Myers Squibb (Investigator initiated trial), Seattle Genetics/Astellas, Exelexis (Investigator initiated trial), Celldex, Calithera and speaker fees from Onclive and Clinical Care Options.

G Sonpavde has received consultancy/advisory fees from Bayer, Sanofi, Pfizer, Novartis, Eisai, Janssen, Amgen, AstraZeneca, Merck, Genentech, Argos, EMD Serono, and Agensys/Astellas; Institutional Research Support from Bayer, Onyx, Celgene, Boehringer-Ingelheim, Merck, Pfizer, Sanofi, Janssen, AstraZeneca, and BMS and speaker fees from Clinical Care Options, Physicians Education Resource (PER), Research to Practice (RTP) and Onclive.

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.