Therapeutic Plasma Exchange With Enfortumab Vedotin and Pembrolizumab for Treatment of Bladder Cancers

This phase II trial compares therapeutic plasma exchange followed by enfortumab vedotin and pembrolizumab to standard of care next-line therapy for the treatment of patients with bladder or upper urinary tract cancers that have spread from where they first started (primary site) to other places in the body (metastatic) and that have not responded to previous treatment (refractory). TPE is a process that slowly removes a patient's blood through an intravenous or central line. The blood is sent through a machine that separates the plasma (the liquid part of blood) from other blood components (red cells, white cells, platelets). The plasma is then removed. The remaining blood components are combined with replacement fluid and returned to the patient's bloodstream through the intravenous or central line. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Treatment with enfortumab vedotin and pembrolizumab is already approved by the Food and Drug Administration for the treatment of bladder cancer, but TPE is not. Combining TPE with enfortumab vedotin and pembrolizumab may work better than standard of care options for treating metastatic and refractory bladder and urinary tract cancers. This study also evaluates the effect of TPE with standard of care antibody drug conjugates (ADCs) in treating patients with refractory metastatic bladder cancer. ADC therapy is treatment with a monoclonal antibody linked to a chemotherapy drug. It is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, and delivers chemotherapy to kill them. Giving TPE with standard of care ADC therapy may be effective in treating patients with refractory metastatic bladder cancer.

NCT Number	NCT07087860
Lead Sponsor	Mayo Clinic
Conditions	Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis and Ureter Urothelial Carcinoma, Refractory Bladder Urothelial Carcinoma, Refractory Renal Pelvis and Ureter Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v7, Stage IV Renal Pelvis and Ureter Cancer AJCC v7
Enrollment	70 participants
Start Date	2025-08-01
Primary Completion	2028-08-07 (estimated)
Study Completion	2028-08-07 (estimated)
Updated on ClinicalTrials.gov	2026-05-08