Neoadjuvant/Adjuvant GVAX Pancreas Vaccine (With CY) With or Without Nivolumab and Urelumab Trial for Surgically Resectable Pancreatic Cancer

Immunotherapy is an innovative approach being developed for the treatment of pancreatic
cancer, a lethal and relatively chemotherapy-resistant disease. However, the tumor and its
environment have developed a number of ways in which they inhibit the function of the immune
system preventing it from recognizing and killing the cancer. In addition, the investigators
still do not understand how T cells, the cells in the immune system that have the potential
to recognize cancer as different and kill cancer cells, traffic into the tumor to accomplish
their task. The investigators are currently testing an immune system activating pancreatic
cancer vaccine (known as GVAX) in combination with immune boosting doses of the chemotherapy
agent, cyclophosphamide, as preoperative and postoperative treatments for pancreatic cancer.
The investigators have discovered tertiary lymphoid aggregates, a unique lymph node-like
structure formed within resected tumors from the patients who received the vaccine two weeks
prior to the surgery. This discovery demonstrates that the immune system can get into the
tumor and provides the investigators with the opportunity to better understand how these
immune cells traffic into the tumor and function once they arrive. The investigators also
found that the vaccine causes an increase in signals that would suppress the immune system's
ability to fight off cancer cells, including signals involving PD-1. In this novel study, the
investigators will test the effects of blocking PD-1 in combination with the vaccine in
patients with pancreatic cancer. The investigators will specifically isolate these immune
cells and evaluate at both the genetic and protein level, the types of signals expressed by
these aggregates. The investigators will compare aggregates from patients with long term
survival versus patients who succumb to their cancer early. In this way, the investigators
will be able to determine how safe this novel treatment is, how effective it is at changing
the immune system in pancreatic cancer, and how it impacts the health and survival of
pancreatic cancer patients who undergo surgery to remove the cancer.

Inclusion Criteria:

1. Newly diagnosed adenocarcinoma of the head, neck, or uncinate process of the pancreas

- Stage I or II disease

2. Surgically resectable disease (R0 or R1) by spiral CT scan

- No distant metastases

3. ECOG Performance Status of 0 to 1

4. Adequate organ function as defined by study-specified laboratory tests

5. Must use acceptable form of birth control

6. Signed informed consent form

7. Willing and able to comply with study procedures

Exclusion Criteria:

1. Currently have or have history of certain study-specified heart, liver, kidney, lung,
neurological, immune, psychological or other medical conditions

2. 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 erythematosus (SLE) autoimmune vasculitis
(e.g., Wegener's Granulomatosis), CNS or motor neuropathy considered to be of
autoimmune origin (e.g., Guillian-Barre Syndrome, Myasthenia Gravis, Multiple
Sclerosis)

3. Patients who have been diagnosed with another cancer in the past 5 years (except for
superficial bladder cancer, non-melanoma skin cancers, or a low grade prostate cancer
not requiring therapy)

4. Patients who have received therapy for pancreatic cancer

5. Using systemically active steroid use

6. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C

7. Patients on home oxygen

8. Patients with oxygen saturation of <92% on room air by pulse oximetry

9. Pregnant or lactating

10. Conditions, including alcohol or drug dependence, or intercurrent illness that would
affect the patient's ability to comply with study visits and procedures