| Eligibility |
Inclusion Criteria:
1. Age =18 years
2. Histologically confirmed locally advanced unresectable (T4b or N2/N3 disease) or
metastatic urothelial cancer (including renal pelvis, ureters, urinary bladder,
urethra).
3. Eligible patients must have had either:
1. Progressed after treatment with at least 1 prior platinum-containing regimen,
(e.g., received at least 2 cycles of cisplatin or carboplatin-based regimen) for
inoperable locally advanced unresectable or metastatic urothelial carcinoma, OR
OR
2. Experienced disease progression or recurrence within 12 months of completion of
neoadjuvant or adjuvant cisplatin-based chemotherapy, OR OR
3. Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology
group (ECOG) performance status 2, grade =2 neuropathy, GFR<60 mL/min, grade =2
hearing loss or New York Heart Association class III or worse congestive heart
failure.
4. Declined platinum (cisplatin or carboplatin) based chemotherapy after informed
discussion with the treating investigator
4. Available pretreatment baseline tumor specimen or willingness to undergo biopsy of
primary or metastatic lesion if archived specimen is not available.
5. ECOG performance status of =2
6. At least one measurable lesion by RECIST version 1.1
7. Patients who are able to understand and sign the informed consent form.
8. Ability to comply with protocol
9. Adequate hematologic and end-organ function per protocol
10. For women of childbearing potential: Negative serum or urine pregnancy test at
screening.
11. For both male and female subjects: agreement to remain abstinent (refrain from
heterosexual intercourse) or use highly effective contraceptive methods that result in
a failure rate of <1% per year during the treatment period and for at least 30 days
after the last dose of study drug
Exclusion Criteria:
1. Concurrent systemic treatment with an anticancer treatment or investigational drug
within 28 days. Palliative radiation to symptomatic primary tumor or metastases is
permitted as long as there are other measurable lesions present outside of the
radiation field.
2. Prior therapy with anti-PD-1 or PD-L1 agents.
3. Concurrent systemic therapy with corticosteroids (>10 mg prednisone equivalent) or
other immunosuppressive agents within 28 days before starting trial drug. Short-term
administration of systemic steroids (less than 7 days), adrenal replacement steroid
doses (=10 mg daily prednisone equivalent), topical, intranasal and inhaled steroid
use is permitted.
4. Patients with untreated or symptomatic central nervous metastases will be excluded.
Patients appropriately treated with either surgery and/or radiation therapy will be
eligible to participate in the study 4 weeks after completion of radiation/surgery and
if follow up brain imaging after CNS directed therapy demonstrates stability or
improvement in brain metastases.
5. Active second malignancy or previous history of malignant disease (other than
urothelial carcinoma) diagnosed within the last 3 years, with the exclusion of basal
or squamous cell carcinoma of the skin, cervical carcinoma in situ and pT2 prostate
adenocarcinoma with Gleason score =7 (with no dominant pattern 4).
6. Prior organ transplantation, including allogenic stem-cell transplantation.
7. Known history of HBV infection (including acute and chronic infection) and untreated
hepatitis C. Patients with treated HCV infection will be eligible.
8. Known hypersensitivity to monoclonal antibody or any biologic drug, history of
anaphylaxis, or uncontrolled asthma.
9. Persisting toxicity related to prior therapy that was > grade 1 according to NCI-CTCAE
v4; grade =2 sensory neuropathy is allowed.
10. Pregnant or lactating, or intending to become pregnant during the study
a. Women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or
surgically sterile must have a negative pregnancy test result within 14 days prior to
the first dose of study treatment.
11. Diagnosis of active autoimmune disease requiring systemic immunosuppression. Patients
with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring
systemic immunosuppression are eligible.
12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan.
a. History of radiation fibrosis in the radiation field (fibrosis) is permitted.
13. Active infection requiring systemic therapy.
14. Severe infections within 4 weeks prior to the first dose of study treatment, including
but not limited to hospitalization for complications of infection, bacteremia, or
severe pneumonia
15. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of
study treatment, within 5 months following the administration of the last dose of
study drug, or anticipation that such a live/attenuated vaccine will be required
during the study.
16. Other severe acute or chronic medical conditions including immune colitis,
inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
conditions including recent (within the past year) or active suicidal ideation or
behavior; or laboratory abnormalities that may increase the risk associated with study
participation or study treatment administration or may interfere with the
interpretation of study results and, in the judgment of the investigator, would make
the patient inappropriate for entry into this study.
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