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

Summary

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.

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

Interventions

OTHER

Best Practice

Receive standard of care

PROCEDURE

Biospecimen Collection

Undergo collection of blood and urine samples

PROCEDURE

Central Venous Cannula Insertion

Undergo central line placement

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

DRUG

Enfortumab Vedotin

Given IV

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

BIOLOGICAL

Pembrolizumab

Given IV

PROCEDURE

Plasmapheresis

Undergo TPE

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

OTHER

Questionnaire Administration

Ancillary studies

BIOLOGICAL

Antibody-Drug Conjugate Therapy

Given IV

Sponsors & Collaborators

• Mayo Clinic

  lead OTHER

Principal Investigators

• Jacob J. Orme, MD, PhD · Mayo Clinic

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-08-01

Primary Completion

2028-08-07

Completion

2028-08-07

FDA Drug

Yes

Countries

• United States

Study Locations