Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

Inclusion Criteria: EV monotherapy main cohort: * Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1 * Planned to receive EV as standard treatment for advanced urothelial cancer * ECOG performance status 0-2 * Prior systemic therapy must have completed at least 14 days prior to initiating therapy. * Age \> 18 years. * Ability to understand and willingness to sign a written informed consent and HIPAA consent document * Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin-fixed paraffin-embedded \[FFPE\] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable. * Normal organ and marrow function as defined below. * Absolute neutrophil count \> 1,000/mm3 unless patient has constitutional neutropenia * Platelets \> 100,000/ul * Hemoglobin \> 8.0 g/dL * Alanine transaminase (ALT) and aspartate transaminase (AST) \<2.5X upper limit of normal (ULN) or \<3.5X ULN if liver metastases * Creatinine Clearance \>20 ml/min EV/pembrolizumab arm: * Patients must have histologically a…