Cryoablation With Pembrolizumab Or Avelumab In Urothelial Carcinoma

Inclusion Criteria:

* The subject has read, signed and dated the Informed Consent Form (ICF), having been advised of the risks and benefits of the trial in a language understood by the subject.
* Age \> 18 years at date of ICF signature having the ability to comply with the protocol.
* Proof of medical insurance coverage.
* Histologically or cytologically documented metastatic (M1, Stage IV) urothelial carcinoma (including renal pelvis, ureters, urinary bladder, urethra)
* Measurable metastatic disease with at least one site of metastatic disease \> 2 cm in size and amenable to percutaneous image-guided cryoablation based on routine Interventional Radiology criteria. Metastasis sites amenable to cryoablation to include lymph node, peritoneum, liver, soft tissue, adrenal glands, kidney, lung, and bone. Must have measurable disease (by RECIST v1.1) independent of the lesion to be ablated (ie patient must have more than one metastasis)
* Life expectancy \> 12 weeks.
* PS ECOG 0 or 1
* Laboratory requirements:

  * ANC \> 1 x 109/L
  * Platelets \> 75 x 109/L
  * ALT / AST \< 5 x ULN
  * Total bilirubin \<3 mg/dL
  * INR \<1.7
  * CrCl \>30 ml/min

Exclusion Criteria:

* Lesion to undergo cryoablation cannot have had prior radiation therapy or other locoregional therapy
* Inability to lie flat for the cryoablation procedure.
* Known significant immunodeficiency due to underlying illness (e.g. HIV / AIDS) and/or blood CD4+ T cells \<200/ul
* History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjogren's syndrome, Guillain- Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
* Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this trial.
* Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this trial.
* Patients with history of vitiligo and controlled psoriasis are eligible for the trial.
* Continued adverse events from a previously administered chemotherapeutic agents.

Grade 1 adverse events and ongoing toxicities such as alopecia are exempt

* Treatment with systemic corticosteroids exceeding the equivalent of 10 mg/day of prednisone or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
* Patients who receive acute, low-dose, systemic corticosteroid medications (e.g., a onetime dose of dexamethasone for nausea) or for prevention of hypersensitivity reactions to contrast agents may be enrolled in the trial.
* Anticoagulant or anti-platelet medication that cannot be interrupted prior to cryoablation
* Pregnant or lactating
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or that could affect the interpretation of the results or render the patient at high risk from treatment complications.
* Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents (including but not limited to IFNs, interleukin \[IL\]-2) within 6 weeks or five half- lives of the drug, whichever was shorter, prior to Day 1.
* Signs or symptoms clinically significant of infection within 2 weeks prior to Day 1.
* Any other systemic anti-cancer treatment (including investigational agents) within 4 weeks prior to the first dose of study drug. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible