Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer

Inclusion Criteria: Patients will be included in the study if they meet all of the following criteria: 1. Patients with age ≥ 20 years old 2. Histologically confirmed pancreatic adenocarcinoma 3. Unresectable locally advanced, recurrent or metastatic diseases ineligible or unsuitable for further surgical or radiation interventions 4. Documented disease progression within 6 months after standard chemotherapies or no available standard chemotherapy. The standard chemotherapies include gemcitabine, nab-paclitaxel, S-1, and FOLFIRINOX. Patient who has prior anti-PD1/anti-PD-L1 treatment will not be eligible. 5. ECOG Performance Status 0-2 6. Documented measurable disease as defined by RECIST v1.1 7. Adequate hematologic parameters, and hepatic and renal functions defined as 1. absolute neutrophil count ≥ 1,000/μL 2. platelets ≥ 75,000/μL 3. total bilirubin ≤ 2.5X ULN (≤ 5X ULN if attributable to liver metastases) 4. AST/ALT ≤ 2.5X ULN (≤ 5X ULN if attributable to liver metastases) 5. serum creatinine ≤ 2 mg/dL or creatinine clearance ≥ 30 mL/min (by calculated or 24-hour urine collection) 8. Normal ECG or ECG without any clinical significant findings 9. Able to understand and sign an informed consent (or have a legal representative who is able to do so) Exclusion Criteria: Patients will be excluded from the study if they meet any of the following criteria: 1. History of allergic reaction to all-trans retinoic acid or nivolumab 2. Patient with liver cirrhosis with Child-Pugh score ≥ 8 (Late Child-Pugh B and Child-Pugh C) 3. Active CNS metastasis defined by clinical symptoms, cerebral edema, steroid or anti-convulsant requirement, or progressive growth. Patients with a history of CNS metastasis or cord compression are allowed in the study if they have been treated and are clinically stable 4. With clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion or diarrhea \> grade 1 5. With uncontrolled intercurrent illness that could limit study compliance or judged to be ineligible for the study by the investigators including, but not limited to, any of the following: 1. ongoing or active infection requiring antibiotic treatment 2. symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia 3. psychiatric illness or social situation that would preclude study compliance 6. Pregnant or breast feeding women (a urine pregnancy test must be performed on all patients who are of childbearing potential before entering the study, and the result must be negative) 7. Patients taking the following medications: immunosuppressants, corticosteroids with the exception of administration topically (e.g., external, intra-articular, intranasal, ophthalmic, or inhalational use) or temporarily (e.g., for treatment or prophylaxis of contrast medium allergy or adverse events), antitumor therapies (e.g., chemotherapies, molecular-targeted therapies, immunotherapies), radiopharmaceuticals with the exception of diagnostic purposes, transplant therapies, vitamin A, antifibrinolytic agents (tranexamic acid, aminocaproic acid, aprotinin), inducers (rifampicin, glucocorticoids, phenobarbital and pentobarbital) or inhibitors (ketoconazole, cimetidine, erythromycin, verapamil, diltiazem and cyclosporine) of the hepatic P450 system, and other unapproved drugs (e.g., investigational use of drugs, unapproved combined formulations, unapproved dosage forms).