Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer

Inclusion Criteria

• Patients diagnosed with platinum-refractory metastatic urothelial cancer that is measureable based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.36 Platinum-refractory disease is defined as progressive disease on cisplatin or carboplatin therapy or within 12 months of prior platinum treatment (last dose.)
• At least 1 prior chemotherapy regimen containing cisplatin or carboplatin
• Patient must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 months (168 days) prior to initiation of treatment on Day 1. Archived specimen can be used for subjects, if available
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Adequate organ function as defined below:
• Absolute neutrophil count (ANC) >= 1, 500 /mcL
• Platelets >= 80,000 / mcL
• Hemoglobin >= 9 g/dL without transfusion dependency
• Serum creatinine = = 35 mL/min for subject with creatinine levels > 1.5 X institutional ULN
• Serum total bilirubin = 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = = 2.5 mg/dL
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria

• Currently receiving or has had treatment with an investigational agent or used an investigational device within 4 weeks of study day 1
• Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-programmed cell death-ligand 2 (PD-L2) agent. Prior therapy with paclitaxel or docetaxel
• Hypersensitivity to pembrolizumab, any of its excipients, paclitaxel, or any of its excipients
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Known history of active TB (Bacillus tuberculosis)
• Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated