Study of Nivolumab in Patients With Advanced Refractory Biliary Tract Cancers

Inclusion Criteria

• Must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease. Patients with ampullary carcinoma are not eligible.
• Must have failed or are intolerant to one line of systemic treatment but no more than 2 prior lines of systemic chemotherapy for advanced BTC. Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible. If the patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing or having intolerance to one line of systemic chemotherapy used to treat the disease recurrence.
• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1.
• Must have radiographic measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Life expectancy of at least 12 weeks (3 months).
• For patients who have received prior radiation, cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met: 28 days have elapsed since that therapy; Lesions that have not been treated with local therapy must be present and measureable.
• Must be able to understand and be willing to sign the written informed consent form. Must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study requirements.
• All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF) except for alopecia.
• Adequate bone marrow, liver and liver function.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L or equivalent units of HCG) performed within24 hours prior to the start of nivolumab Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
• Men and women of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 3 months after the last dose of study drug.
• Patients with history of hepatitis B and hepatitis C will be eligible but patients with hepatitis B must be started on antiviral therapy prior to beginning study therapy.
• Availability of archival tumor tissue for biomarkers analysis (FFPE block or cell block will be required).

Exclusion Criteria

• Active central nervous system (CNS). If CNS metastases are treated and potential participants are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a Brain MRI prior to enrollment. Must be off corticosteroids or on a dose of less than 10 mg per day.
• Active, known or suspected autoimmune disease. Potential participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
• Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanom