1. Age ≥18 years.
2. Have histologically or cytologically proven cholangiocarcinoma or adenocarcinoma of
the pancreas that is metastatic or unresectable.
3. ECOG performance status 0 or 1
4. Life expectancy of greater than 12 weeks.
5. Patients must have adequate organ and marrow function defined by study-specified
6. Woman of child bearing potential must have a negative pregnancy test.
7. Must have progressive measurable disease.
8. Must have an accessible non-bone tumor that can be biopsied.
9. Must use acceptable form of birth control while on study.
10. Willing to provide tissue and blood samples.
11. Ability to understand and willingness to sign a written informed consent document.
1. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 3 weeks
prior to trial registration
2. Prior treatment with epigenetic therapy (such as entinostat, panobinostat, vorinostat,
romidepsin, 5-azacitidine, or decitabine)
3. Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CTLA4, etc.).
4. Hypersensitivity reaction to any monoclonal antibody.
5. History of any autoimmune disease: inflammatory bowel disease, (including ulcerative
colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis
(scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g.,
Wegener's Granulomatosis), CNS or motor neuropathy considered to be of autoimmune
origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis).
Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger (precipitating event).
6. Have significant and/or malignant pleural effusion
7. Has a pulse oximetry < 92% on room air.
8. Known history or evidence of brain metastases.
9. Conditions, including alcohol or drug dependence, intercurrent illness, or lack of
sufficient peripheral venous access, that would affect the patient's ability to comply
with study visits and procedures.
10. Are pregnant or breastfeeding.
11. Infection with HIV or hepatitis B or C.
12. Patients on immunosuppressive agents.
13. Requiring concurrent administration of valproic acid.
14. Patients with diverticulitis, intra-abdominal abscess, or GI obstruction
15. Any contraindication to oral agents.
16. Another active malignancy ≤ 3 years prior to registration with the exception of
non-melanotic skin cancer or carcinoma-in-situ of any type.
17. Unwilling or unable to follow the study schedule for any reason.
18. Evidence of ascites on imaging.