The purpose of this clinical trial is to study an experimental drug called pembrolizumab or MK-3475 for use in combination with chemotherapy and radiation therapy for patients with resectable (surgical removal) or borderline resectable pancreatic cancer. In general, pancreatic cancer that cannot be removed by surgery is sometimes treated with chemotherapy and radiation therapy, called neoadjuvant treatment, to shrink the tumor so that surgery might be possible. However, this is not always effective at shrinking the tumor enough to allow it to be removed with surgery. Recent discoveries suggest that the investigators own immune system might have a role in controlling the growth of tumors. Drugs such as pembrolizumab can stimulate the immune system against cancer. The purpose of this study is to investigate whether pembrolizumab can be used safely during neoadjuvant treatment and can improve the body's immune response against pancreatic cancer.

Pembrolizumab has been approved for treatment of patients with melanoma but has not been proven to be safe or helpful in patients with pancreatic cancer and is not approved by the U.S. Food and Drug Administration (FDA) for this purpose.

Inclusion Criteria:

1. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.
2. Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
3. Adequate organ function
4. In subjects requiring biliary decompression, metal stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed

Exclusion Criteria:

1. Immunodeficiency or taking steroid or any other form of immunosuppressive therapy
2. Has a plastic biliary stent for decompression
3. Metastatic disease
4. Prior treatment for pancreatic cancer (other than 4-8 cycles of Folfirinox) or prior treatment with radiation for other diagnoses to the expected pancreatic cancer treatment area
5. Active autoimmune disease
6. Pregnancy or Nursing
7. Known history of Human Immunodeficiency Virus (HIV) or Hepatitis B or C
8. Prior monoclonal antibody within 4 weeks prior to study Day 1
9. Known additional malignancy that is progressing or requires active treatment
10. Evidence of interstitial lung disease or active, non-infectious pneumonitis
11. Active infection requiring systemic therapy
12. Prior therapy with an anti-Program Death (PD-1) antibody, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody