Padcev (enfortumab vedotin-ejfv)

Nectin-4 expression in the prostate is heterogeneous and context-dependent, with higher levels in benign glands within cancer-bearing prostates and lower levels with advancing tumor stage and nodal/metastatic spread. These findings provide an expression map of nectin 4 across benign and malignant prostate compartments and disease stages and may inform future exploratory enrichment strategies for nectin-4-targeted therapies.

Personalized, tumor-informed ctDNA testing can indicate response to EV±P and is prognostic of survival benefit in patients with la/mUC receiving EV±P.

P1/2, N=27, Not yet recruiting, Fred Hutchinson Cancer Center

P1/2, N=78, Not yet recruiting, Astellas Pharma Global Development Inc.

P2, N=56, Not yet recruiting, The Netherlands Cancer Institute

P2, N=58, Recruiting, Peking University Third Hospital

We describe a 57-year-old man receiving EV and pembrolizumab who developed profound insulin-resistant DKA that persisted despite standard therapy. Following initiation of induction alongside continued insulin therapy, resolution of ketoacidosis occurred within 46 hours. This case illustrates a pharmacokinetic-informed approach to EV-associated refractory DKA and highlights how understanding drug metabolism may improve therapeutic outcomes when conventional therapy is insufficient.

P2, N=39, Not yet recruiting, University of Florida

P2, N=28, Recruiting, Mayo Clinic | Trial completion date: Nov 2026 --> Jun 2028 | Trial primary completion date: Nov 2026 --> Jun 2028

A 64-year-old man with metachronous metastatic urothelial carcinoma originating from the right renal pelvis underwent nectin-4-targeted [68Ga]Ga-NECT-224 PET/CT prior to initiation of nectin-4-targeted antibody-drug conjugate (ADC) therapy with enfortumab-vedotin (PADCEV), in combination with pembrolizumab. Subsequent [68Ga]Ga-NECT-224 PET/CT restaging revealed multiple new lesions with intense nectin-4 expression. This case illustrates the potential of [68Ga]Ga-NECT-224 PET/CT to visualize heterogeneous nectin-4 expression, its potential in therapy guidance, and highlights the need for theranostic strategies in patients retaining target expression despite cytotoxic therapy resistance.

Conventional chemotherapy and first-generation antibody-drug conjugates (ADCs), such as ado-trastuzumab emtansine (T-DM1), were limited by non-specific cytotoxicity, heterogeneous drug-antibody ratios, linker instability, and insufficient bystander killing, yielding modest efficacy in heavily pretreated populations...Clinically, trastuzumab deruxtecan demonstrated meaningful progression-free survival benefit in HER2-low metastatic breast cancer, while enfortumab vedotin reduced mortality risk in platinum- and immunotherapy-refractory urothelial carcinoma, establishing ADC efficacy across solid tumor histologies...Trastuzumab deruxtecan carries a 15.4% incidence of interstitial lung disease, including fatal events, and sacituzumab govitecan is associated with grade 3 or higher neutropenia in approximately 51% of patients. Furthermore, next-generation ADCs are not resistance-proof, with antigen downregulation, payload efflux, and impaired internalization emerging as clinically relevant escape mechanisms. Biomarker-driven patient selection, rigorous toxicity monitoring, and prospective trials addressing resistance will be essential to realizing the full and durable potential of this drug class.