This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and SBRT (focused radiation) is effective (anti-tumor activity) and safe in patients with locally advanced pancreatic cancer.

Inclusion Criteria:

1. Locally advanced pancreatic adenocarcinoma
2. Patients must have received mFOLFIRINOX or Gemcitabine/ Abraxane based chemotherapy for 4 cycles with last dose of therapy between 2-5 weeks of study enrollment.
3. Age >18 years
4. No metastatic disease
5. ECOG Performance Status of 0 to 1
6. Adequate organ function as defined by study-specified laboratory tests
7. Patients must be able to have fiducials placed for SBRT
8. Must use acceptable form of birth control through the study
9. Signed informed consent form
10. Willing and able to comply with study procedures

Exclusion Criteria:

1. Patients who have been off of mFOLFIRINOX or gemcitabine/abraxane therapy for more than 49 days
2. Patients who have had more than one line of chemotherapy
3. Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements
4. Patient who have had prior treatment with IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
5. Patients receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days prior to first dose of study drug
6. Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 14 days of study drug administration
7. Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematous (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin.
8. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
9. Patients with evidence of interstitial lung disease
10. Patients on home oxygen
11. Patients with oxygen saturation of <92% on room air by pulse oximetry
12. Pregnant or lactating
13. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures