Padcev (enfortumab vedotin-ejfv)

P1/2, N=348, Terminated, Astellas Pharma Global Development, Inc. | Trial completion date: Sep 2026 --> Feb 2026 | Active, not recruiting --> Terminated; Sponsor stopped the study after meeting enrollment targets and primary objectives, and after collecting sufficient data for planned regulatory filings. The decision was not due to safety concerns, futility, or any regulatory request.

P2, N=60, Active, not recruiting, Fox Chase Cancer Center | Recruiting --> Active, not recruiting

P1, N=37, Not yet recruiting, Generate Biomedicines

P1/2, N=49, Completed, Merck Sharp & Dohme LLC | N=37 --> 49

Over the past decade, multiple ICIs have demonstrated meaningful clinical activity, and their indications have expanded across treatment lines, including second-line therapy after platinum, first-line therapy for cisplatin-ineligible disease, avelumab maintenance following chemotherapy, and, more recently, combination strategies such as pembrolizumab plus enfortumab vedotin. In this review, we provide a comprehensive overview of currently established and emerging biomarkers of ICI response in UBC, including PD-L1 immunohistochemistry, serum inflammatory markers, tumor mutational burden, histology and molecular subtypes, gene expression patterns and microbiome features. We discuss their strengths, limitations, and potential translational relevance, highlighting ongoing challenges and future directions.

P2, N=240, Not yet recruiting, Astellas Pharma Global Development, Inc.

The Food and Drug Administration (FDA)-approved Nectin-4-targeted drug, enfortumab vedotin, has demonstrated substantial efficacy in the treatment of UC...In treatment experiments, covalent 177Lu-FZ-NRs strongly inhibited tumor growth without obvious toxicity. In summary, our novel Nectin-4-targeted covalent bicyclic peptide radioligands provide new molecular imaging tools for the non-invasive assessment of Nectin-4 and establish a foundation for UC-targeted radiotherapy.

Recent advances highlight a rapid surge in positive immunotherapy trials across different head and neck cancer entities, with clinical benefit observed both when immune checkpoint inhibitors are moved earlier in the disease course and when they are combined with agents targeting resistance mechanisms or enabling more precise drug delivery to tumors.

P1/2, N=390, Completed, Merck Sharp & Dohme LLC | Recruiting --> Completed

We found that tumor samples from patients with cancer of the urinary tract that had spread to the brain had higher expression of a gene called NECTIN4 (67%). Our findings suggest that treatments targeting NECTIN4, such as a drug called enfortumab vedotin with or without pembrolizumab, might benefit patients with brain metastases, especially if their tumors have high NECTIN4 levels.

Using plasma alone, APEX enables classification of prognostically relevant basal and classical pancreatic cancer subtypes and identifies plasma-inferred NECTIN4 expression as a biomarker of response to enfortumab vedotin in metastatic bladder cancer. Together, these findings establish APEX as a biopsy-free approach for profiling tumor transcriptional states and extend liquid biopsy beyond genomic alterations to clinically relevant gene expression programs.

Enfortumab vedotin, sacituzumab govitecan, and HER2-directed ADCs have demonstrated meaningful clinical activity across metastatic and earlier disease settings, with enfortumab vedotin plus pembrolizumab now established as a first-line standard of care. We discuss emerging biomarkers beyond antigen abundance, patterns of cross-resistance and treatment sequencing, and evolving strategies to overcome resistance, including next-generation ADC design and rational combination therapies. Advancing biomarker-driven patient selection and addressing mechanisms of resistance will be critical to maximizing the durability and clinical impact of ADCs in urothelial carcinoma.