Background 

Two newer treatments for advanced bladder cancer are showing great promise. One is Enfortumab Vedotin (EV), a drug that targets a protein found on bladder cancer cells, and the other is pembrolizumab (often called “pembro”), an immunotherapy that helps the body’s own defenses attack cancer. When used together, EV and pembro are even more effective at slowing tumor growth than when either is used alone. 

However, because these treatments are still new for bladder cancer, doctors don’t yet know how to tell early on whether they are working in patients. They also don’t fully understand why the cancer eventually becomes resistant to these drugs in some cases. 

What This Research Proposes to Address 

Researchers have already found in mice that EV can activate the immune system, much like pembro does. In this study, the team will examine blood samples from patients receiving EV, pembro, and the combination of both. By looking at how immune cells change during treatment, they hope to find “biomarkers”—signals in the blood that show the drugs are working. 

The researchers are also collecting tumor samples from patients in a clinical trial who are receiving EV and pembro before surgery. By studying tumors from patients whose cancer stops responding, they will look for changes in the cancer cells and in the immune cells within the tumors. For example, they will check whether the cancer reduces or changes its levels of Nectin-4, the protein that EV needs to attach to and kill bladder cancer cells. 

Why This Research Is Important 

If scientists can identify reliable biomarkers in the blood, doctors will have an easier and less invasive way to track whether patients are benefiting from EV and pembro. This could also help match the right patients to the right treatment more quickly. 

Studying why tumors become resistant is equally important. If researchers can discover the exact changes in bladder tumors and immune cells that make these drugs stop working, they can guide the development of new therapies to overcome resistance. 

Ultimately, this project could help improve how patients are monitored on EV and pembro, and it may lead to stronger, longer-lasting treatments for advanced bladder cancer. 

Gupta, A., Sevilla, C., Pihlstrom, N. L., Liang, S., Regazzi, A. M., McCoy, A. S., Maher, C. A., Wong, P., Ahmed, F., Funt, S. A., Iyer, G., Bajorin, D. F., Teo, M. Y., Rosenberg, J. E., Osorio, J. C., & Aggen, D. H. (2025). Characterizing the immune effects of enfortumab vedotin (EV) on peripheral blood mononuclear cells (PBMCs) in metastatic urothelial cancer patients (mUC). Journal of Clinical Oncology, 43(5_suppl), 833–833. https://doi.org/10.1200/JCO.2025.43.5_suppl.833

None Reported as of August 2025

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