Inclusion Criteria
Have histologically or cytologically documented locally advanced unresectable or
metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary
bladder, and urethra)
Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of
proinflammatory and immunosuppressive factors
Have ECG with no clinically significant findings as assessed by the investigator
performed within 28 days prior to first dose
Demonstrate adequate organ function
For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate of
1% per year during the treatment period and for at least 5 months after the last dose
of study treatment
Exclusion Criteria
Any approved anti-cancer therapy including chemotherapy, targeted small molecule
therapy or radiation therapy within 2 weeks prior to trial Day 0; or if subject has not
recovered (ie., Less than or equal to grade 1 or returned to baseline level) from
adverse events due to a previously administered agent
Currently participating and receiving trial therapy or has participated in a trial of an
investigational agent and/or has used an investigational device within 28 days prior to
Day 0
Documented active or untreated central nervous system (CNS) metastases and/or
carcinomatous meningitis
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly and more frequently)
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued
use of bisphosphonate therapy or denosumab
Malignancies other than UCa within 3 years prior to Day 0, with the exception of those
with negligible risk of metastasis or death treated with expected curative outcome
(such as adequately treated carcinoma in situ of the cervix, basal or squamous cell
kin cancer, or ductal carcinoma in situ treated surgically with curative intent) or
localized prostate cancer treated with curative intent and absence of prostate-specific
antigen (PSA) relapse or incidental prostate cancer
Pregnant or lactating, or intending to become pregnant or father children within the
projected duration of the trial starting with the screening visit through 5 months after the
last dose of checkpoint inhibitor and/or DNA vaccine
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric
or humanized antibodies or fusion proteins
Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in
Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation
Active or history of autoimmune disease or immune deficiency, 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, Wegener granulomatosis with polyangiitis, Sj?gren?s
yndrome, Guillain-Barr? syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
History or any evidence of interstitial lung disease such as idiopathic pulmonary fibrosis,
organizing pneumonia (e.g., bronchiolitis obliterans), drug induced or active noninfectious
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on
creening chest CT scan
History of HIV
Active hepatitis B or active hepatitis C
Severe infections within 4 weeks prior to enrollment, including, but not limited to,
hospitalization for complications of infection, bacteremia, or the presence of any active
infection requiring systemic therapy
Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0
History or current evidence of any condition, therapy or laboratory abnormality (e.g.
chronic renal failure; angina, myocardial ischemia or infarction, class 3 or higher
congestive heart failure, cardiomyopathy, or clinically significant arrhythmias) that in
the opinion of the treating investigator might confound the results of the trial or interfere
with the subject?s participation for the full duration of the trial
Prior allogeneic stem cell or solid organ transplant
Received a live, attenuated vaccine within 28 days prior to randomization or anticipation
that such a live attenuated vaccine will be required during the trial
Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM
injections, or use of blood thinners (e.g. anticoagulants or antiplatelet drugs) within 2
weeks prior to Day 0