Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

Exclusion Criteria

• •The neuroendocrine histology (small cell and large cell carcinomas) and non-epithelial bladder tumors (e.g. bladder sarcoma, carcinosarcoma, paraganglioma, melanoma, primary lymphoma, and lymphoepithelioma-like carcinoma) are excluded.
• •Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier \[i.e. ongoing clinically significant toxicity (grade 2 or higher with the exception of alopecia) associated with prior treatment\]
• •Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study
• •Patients with ongoing sensory or motor neuropathy grade \>= 2
• •Prior treatment or enrollment in a study with EV or PD1/PD-L1 immune checkpoint inhibitor (including maintenance therapy)
• •Known uncontrolled diabetes mellitus with glycated hemoglobin (HbA1c) \>= 8% or HbA1c 7% to \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
• •Active central nervous system (CNS) metastases
• •Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for localized prostate cancer, definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months
• •Currently receiving systemic antimicrobial treatment for active infection or high dose steroids (\> 10mg of prednisone or equivalent)
• •A FCBP who has a positive urine pregnancy test at baseline or within 72 hours prior to receiving first study dose. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •Breastfeeding females
• •History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), known hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive), known active hepatitis C virus (defined as HCV ribonucleic acid \[mRNA\] \[qualitative\] is detected) or tuberculosis
• •History of active keratitis or corneal ulcerations
• •History of allogenic tissue/solid organ transplant
• •Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias within 6 months prior to first dose of EV/pembrolizumab
• •Other uncontrolled current illness including, but not limited to, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements