A Study of Enfortumab Vedotin in People With Urothelial Carcinoma of the Upper Urinary Tract

The purpose of this study is to find out whether the study drug, enfortumab vedotin, is an effective and safe treatment for people who have urothelial carcinoma of the upper urinary tract. Study participants will be people who are not eligible to receive or have chosen not to receive the chemotherapy drug cisplatin for treatment of their cancer. In addition, all participants will be planning on having standard surgery to remove their tumor.

Inclusion Criteria: * Histologically confirmed high grade urothelial carcinoma of the upper tract and/or radiographically visible tumor stage T2-T4a N0/x M0 disease with positive selective urinary cytology. Hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition. (Variant histology is acceptable if there is a predominant urothelial component. Discussion with PI strongly encouraged.) Retroperitoneal lymph nodes \200, undetectable viral load and on HAART therapy. Exclusion Criteria: * Presence of metastatic disease. * Prior treatment with systemic chemotherapy or radiotherapy for urothelial cancer of the bladder within the last 2 years. (Prior intravesical treatment such as BCG is allowed). * Grade 2 or higher peripheral neuropathy. * Patients with active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator. * Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \ 35 mIU/mL * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness. * Inability to comply with study and/or follow-up procedures.