Pembrolizumab as Maintenance Therapy in Treating Patients with Urothelial Cancer That is Metastatic or Cannot Be Removed by Surgery after First-Line Chemotherapy

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =< 1 within fourteen days of registration for protocol therapy
• Histological or cytological evidence of urothelial cancer of the bladder, urethra, ureter, or renal pelvis; differentiation with variant histologies (e.g., squamous cell differentiated) will be permitted provided that the predominant histology is urothelial carcinoma
• Metastatic and/or unresectable (cT4b) disease
• Must have achieved an objective response (CR/PR) or stable disease (SD) upon completion of scheduled treatment
• Subjects may have had up to 8 cycles of standard first-line platinum-based chemotherapy for mUC (e.g., as per National Comprehensive Cancer Network [NCCN] guidelines); able to commence study treatment within 2 to 6 weeks of receiving last dose of first-line chemotherapy
• All subjects must have adequate archival tissue available prior to registration (i.e., at least 20 unstained slides or paraffin block); if acceptable archival tissue is not available, the subject must be willing to consent to providing a core or excisional biopsy for research prior to registration for protocol therapy; if archival tissue is not available and there are no sites amenable to biopsy, enrollment must be discussed with the sponsor-investigator on a case by case basis
• Absolute neutrophil count (ANC) >= 1,500/mcL (must be obtained within 14 days prior to registration for protocol therapy)
• Platelets >= 100,000/mcL (must be obtained within 14 days prior to registration for protocol therapy)
• Hemoglobin >= 8.5 g/dL (must be obtained within 14 days prior to registration for protocol therapy)
• Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for subject with creatinine levels > 1.5 x institutional ULN (must be obtained within 14 days prior to registration for protocol therapy) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (must be obtained within 14 days prior to registration for protocol therapy)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (must be obtained within 14 days prior to registration for protocol therapy)
• International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy; if subject on anticoagulant therapy, PT or PTT must within therapeutic range of intended use of anticoagulants (must be obtained within 14 days prior to registration for protocol therapy)
• Female subjects of childbearing potential must have a negative serum pregnancy within three days prior to registration for protocol therapy
• Sexually active, pre-menopausal women of childbearing potential must be willing to use an adequate method of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > one year
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug

Exclusion Criteria

• More than one line of prior chemotherapy for metastatic or locally advanced disease with the following exception: * Prior neoadjuvant/adjuvant chemotherapy will not count as line of therapy if completed greater than 12 months prior to initiation of chemotherapy regimen for metastatic or unresectable disease
• Current or past participation in a study of an investigational agent or using an investigational device within four weeks of registration for protocol therapy
• Diagnosis of immunodeficiency or is receiving treatment with systemic steroid therapy or any other form of immunosuppressive therapy within seven days prior to registration for protocol therapy
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within two weeks prior to registration for protocol therapy; Note: If the subjects have undergone major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting protocol therapy
• Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to registration for protocol therapy and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least seven days prior to registration for protocol therapy
• Active autoimmune disease requiring systemic treatment within the past three months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; exceptions include: subjects with vitiligo or resolved childhood asthma/atopy; subjects who require intermittent use of bronchodilators or local steroid injections, and subjects with hypothyroidism who are stable on hormone replacement or Sjogren’s syndrome are eligible for the study
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Active infection requiring systemic therapy
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening period through 120 days after the last dose of protocol therapy
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); examples include nivolumab, MPDL3280, etc
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Receipt of a live vaccine within 30 days prior to registration for protocol therapy
• Unresolved toxicity (i.e., > grade 1 or above baseline) due to previously administered agents; exception includes: subjects with =< grade 2 neuropathy are eligible for the study