enfortumab vedotin

Overview

Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) designed to target Nectin-4 (also known as PVRL4), a cell adhesion molecule overexpressed on the surface of various epithelial tumor cells, most notably in urothelial carcinoma and triple-negative breast cancer. The drug consists of a fully human anti-Nectin-4 monoclonal antibody conjugated via a protease-cleavable linker to monomethyl auristatin E (MMAE), a potent microtubule-disrupting cytotoxic agent. Upon binding to Nectin-4 on tumor cell surfaces, the ADC is internalized, the linker is cleaved by lysosomal proteases, and MMAE is released intracellularly to inhibit tubulin polymerization and induce apoptosis.

Enfortumab vedotin received regulatory approval for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have previously received platinum-containing chemotherapy and a programmed death receptor-1 (PD-1) or Programmed Death-Ligand 1 (PD-L1) inhibitor. Its clinical development has since expanded into earlier lines of therapy, perioperative settings, and combination regimens with checkpoint inhibitors such as pembrolizumab, reflecting the drug's broad potential in Nectin-4-expressing malignancies.

Focus of Latest Publications

Recent publications on enfortumab vedotin have focused primarily on its use in metastatic urothelial carcinoma, especially in combination with pembrolizumab. One study examined first-line enfortumab vedotin plus pembrolizumab versus gemcitabine plus cisplatin for metastatic urothelial carcinoma, noting that the combination had recently emerged as the preferred first-line regimen, while also highlighting that evidence from non-trial settings remains limited. Another real-world comparison evaluated avelumab maintenance after platinum-based chemotherapy against enfortumab vedotin plus pembrolizumab, reflecting ongoing interest in how this regimen performs relative to other standard first-line strategies.

Several reports addressed real-world effectiveness and treatment sequencing. A multicenter Japanese study assessed enfortumab vedotin in metastatic urothelial carcinoma using EV-301 trial eligibility stratification and restricted mean survival time analysis to clarify outcomes outside the trial setting. In addition, a real-world comparison of avelumab maintenance and enfortumab vedotin plus pembrolizumab aimed to determine whether maintenance therapy after platinum-based chemotherapy could offer comparable or superior survival outcomes to the enfortumab vedotin-based combination.

Other publications explored perioperative and neoadjuvant applications. A review of neoadjuvant systemic therapy in kidney and bladder cancer described enfortumab vedotin and immune checkpoint inhibitor combinations as expanding treatment options and noted ongoing studies of novel adjuvant approaches, including those guided by postoperative circulating tumor DNA and potentially supported by artificial intelligence-driven digital pathology. A separate report on perioperative enfortumab vedotin and pembrolizumab in bladder cancer focused on patients with muscle-invasive disease who are ineligible for cisplatin-based chemotherapy, for whom perioperative therapy may improve outcomes.

Clinical observations also included a case of node-positive upper tract urothelial carcinoma with pathologic complete response after enfortumab vedotin plus pembrolizumab. This report emphasized that, although EVP is now preferred first-line treatment for locally advanced or metastatic urothelial carcinomas, the optimal duration of therapy and the role of consolidative surgery after complete response remain unclear.

Key Publications

• NEWJul First-Line Enfortumab Vedotin Plus Pembrolizumab vs Gemcitabine Plus Cisplatin for Metastatic Urothelial Carcinoma. (JAMA network open, 2026, PMID 42384383): "Enfortumab vedotin plus pembrolizumab (EV/P) recently emerged as the preferred first-line treatment regimen for metastatic urothelial carcinoma (mUC), but evidence outside trial settings is relatively limited."
• NEWJul Real-world Comparison of Avelumab Maintenance and Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma. (Anticancer research, 2026, PMID 42373274): "This study aimed to determine whether avelumab maintenance following platinum-based chemotherapy offers comparable or superior survival outcomes to EVP."
• May Pathologic Complete Response After Enfortumab Vedotin Plus Pembrolizumab in Node-positive Upper Tract Urothelial Carcinoma. (In vivo (Athens, Greece), 2026, PMID 42049426): "Enfortumab vedotin plus pembrolizumab (EVP) is the preferred first-line treatment for locally advanced or metastatic urothelial carcinomas."
• Apr Neoadjuvant Systemic Therapy in Kidney and Bladder Cancer: Current Evidence and Emerging Paradigms. (American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting, 2026, PMID 41774881): "Enfortumab vedotin and immune checkpoint inhibitors have expanded treatment options, with ongoing studies evaluating novel adjuvant approaches tailored to patients' postoperative circulating tumor DNA."
• Apr Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. (The New England journal of medicine, 2026, PMID 41707170): "Perioperative therapy may improve outcomes in this population."
• May Real-world efficacy of enfortumab vedotin in Japanese patients with metastatic urothelial carcinoma stratified by EV-301 trial eligibility: a multicenter Bayesian restricted mean survival time analysis. (Japanese journal of clinical oncology, 2026, PMID 41603536): "Enfortumab vedotin (EV) exhibited superior efficacy in the EV-301 trial; however, real-world outcomes stratified by trial eligibility criteria remain unclear."