Cabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer

Inclusion Criteria: * Histologically-documented urothelial carcinoma (squamous differentiation or mixed cell types allowed if urothelial carcinoma is present) * Metastatic disease or unresectable locally-advanced disease * Must have received prior treatment with a checkpoint inhibitor (CPI). A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor alone or with any other combination * Must either have prior treatment with platinum-containing chemotherapy or be ineligible at time of enrollment * Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy * Tumor tissue samples must be available for submission prior to initiation of study treatment or patient must be willing to undergo repeat tumor biopsy * Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) * An Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2 * Must be \>= 18 years of age * Absolute neutrophil count (ANC) \>= 1500/uL without granulocyte colony-stimulating factor support (within 28 days before first dose of study treatment) * White blood cell count \>= 2500/uL (within 28 days before first dose of study treatment) * Platelets \>= 100,000/uL without transfusion (within 28 days before first dose of study treatment) * …