SD-101, Nivolumab, and Radiation Therapy in Treating Patients With Chemotherapy-Refractory Metastatic Pancreatic Cancer

Inclusion Criteria

• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 - 2
• •Able and willing to provide written informed consent
• •Pathology confirmed pancreatic adenocarcinoma by histology or cytology
• •Life expectancy \>= 3 months
• •Progression during or after greater than or equal to 1 line of systemic treatment for metastatic pancreatic adenocarcinoma. Patients who do not tolerate 1st line systemic treatment for metastatic pancreatic adenocarcinoma are also eligible
• •\>= 1 metastatic liver lesion amenable for radiation, intratumoral injection, and core biopsy
• •* Lesion for radiation, intratumoral injection, and biopsy may not be a previously irradiated lesion but may have been previously treated with liver directed therapy (e.g., radiofrequency ablation \[RFA\], transarterial chemoembolization \[TACE\], selective internal radiation therapy \[SIRT\], etc.) provided there is radiographic evidence of disease progression in the interim since last local/regional treatment
• •\>= 1 target lesion outside the field of radiation, measurable by RECIST v1.1
• •Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3
• •Platelet count \>= 50,000/mm\^3
• •Hemoglobin \>= 8 g/dL
• •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 5 times upper limit of normal (ULN)
• •Alkaline phosphatase =\< 5 times ULN
• •Total bilirubin =\< 2 times ULN
• •Creatinine =\< 2 times ULN
• •Patients with hepatitis B virus are allowed if antiviral therapy has been given for \> 8 weeks with viral loads \< 100 IU/mL prior to the first dose of trial therapy. Subjects with hepatitis C virus are allowed. Viral loads for hepatitis B and C will be monitored every 4 weeks for patients with active hepatitis B and/or C
• •Women with childbearing potential and males must be willing to use adequate birth control on trial and until 5 months for women or 7 months for men after the last of study therapy
• •Ability to adhere to study schedule and protocol requirements
• •Willing to undergo pre-treatment biopsy and on-treatment biopsy