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.
Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a). (Note: Tissue samples are required.) (Participants with cT3/T4a staged disease will be capped at 25% of patients treated at RP2D).
Urothelial histology present. Mixed histologies other than small cell/neuroendocrine are allowed as long as some urothelial histology is present. Neuroendocrine histology of any component and pure variant (non-urothelial) histology tumors will be excluded. (Patients with < 50% urothelial histology will be capped at 25% of patients treated at RP2D).
Must be judged by the investigator to be ineligible for radical cystectomy or electing not to undergo radical cystectomy.
Must be eligible for and agree to receive bladder irradiation as determined by the treating investigator.
Presence of distant metastases on imaging (M1 disease).
Presence of ≥ N2 disease on imaging (N1 disease allowed, but participants with N1 disease will be capped at 25% of patients treated at RP2D).
Presence of small cell / neuroendocrine histology in tumor sample (any content).
Absence of urothelial histology in TURBT tumor sample (pure variant histology).
University of California, San Francisco
Lead sponsor
Astellas Pharma Inc
Collaborator
Merck Sharp & Dohme LLC
Collaborator