Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer

Summary

This phase Ib/II trial studies the side effects, best dose, and effectiveness of enfortumab vedotin (EV) in combination with pembrolizumab and radiation therapy for treating patients with muscle invasive bladder cancer. Standard of care treatment for muscle invasive bladder cancer is chemotherapy, to shrink the tumor before the main treatment is given (neoadjuvant), followed by surgery to remove all of the bladder as well as nearby tissues and organs (radical cystectomy). In cases where patients are not candidates for the standard of care approach or prefer a bladder sparing option, tri-modality therapy with transurethral resection of bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy is used. 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 tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor 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. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer.

Conditions

• Bladder Cancer
• Muscle-Invasive Bladder Carcinoma
• Stage II Bladder Cancer AJCC v8
• Stage IIIA Bladder Cancer AJCC v8

Interventions

DRUG

Enfortumab Vedotin

Given intravenously (IV)

BIOLOGICAL

Pembrolizumab

Given IV

RADIATION

Intensity Modulated Radiation Therapy (IMRT)

Undergo standard of care, IMRT

PROCEDURE

Transurethral Resection of Bladder Tumor

Undergo TURBT

PROCEDURE

Cystoscopy (CS)

Undergo cystoscopy

PROCEDURE

Computed Tomography (CT)

Undergo CT imaging

PROCEDURE

Magnetic Resonance Imaging (MRI)

Undergo MRI imaging

PROCEDURE

Positron Emission Tomography (PET)

Undergo PET Scan, may be combined with CT (PET/CT)

Sponsors & Collaborators

• Astellas Pharma Inc

  collaborator INDUSTRY

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Vadim Koshkin, MD · University of California, San Francisco

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-31

Primary Completion

2028-01-31

Completion

2028-01-31

FDA Drug

Yes

Countries

• United States

Study Locations