Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas.

The purpose of this study is to evaluate if the combination of nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with GVAX is safe in patients with locally advanced pancreatic cancer (LAPC) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of CD8+CD137+ cells in PDACs .


Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years.
* Patients with histologically- or cytologically-proven, surgically unresectable, locally advanced pancreatic adenocarcinoma.
* If the patient does not have a diagnostic biopsy that is adequate for review at our institution, the patient must agree to a research core biopsy to be performed at Johns Hopkins.
* If the patient's available imaging is not adequate for review by our institution, the patient must agree to a repeat imaging to be performed at Johns Hopkins.
* Patients cannot have had any prior therapy for the locally advanced pancreatic adenocarcinoma.
* ECOG performance status 0 or 1
* Life expectancy greater than 3 months.
* Able to swallow pills or capsules.
* Patient must have adequate organ function defined by the study-specified laboratory tests.
* Patients must be eligible to receive FOLFIRINOX-based chemotherapy.
* Patients must be willing to be treated with stereotactic body radiation therapy (SBRT) only at Johns Hopkins Hospital.
* Patients must be willing to undergo a core biopsy of the pancreatic cancer.
* Patients must be willing to undergo a biopsy of the pancreatic cancer if the patient is not deemed a surgical candidate during the pre-surgical evaluation.
* Must use acceptable form of birth control while on study.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* Have had non-FOLFIRINOX-based chemotherapy for the pancreatic cancer.
* Have received any anti-neoplastic biologics, vaccines or hormonal treatment, including investigational drugs, within 28 days of the first dose of study.
* History of past treatment with immunotherapy agents prior to initial enrollment into this study (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4 or anti-CCR2/5 drugs).
* Have had prior organ or tissue allograft or allogeneic bone marrow transplantation, including corneal transplants.
* Is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer.
* Current use of immunosuppressive medications within 14 days prior to study medications.
* Have received any vaccine within 14 days prior to study medications.
* Receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of the first dose of study medication.
* History of any autoimmune disease. Patients with thyroid disease will be allowed.
* Has a history of (non-infectious) pneumonitis or current pneumonitis.
* Has a pulse oximetry \< 92% on room air.
* Requires the use of home oxygen.
* Patients with uncontrolled intercurrent illness including, but not limited to, myocardial infarction or stroke/transient ischemic attack within the past 6 months, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* 12-lead electrocardiogram with QRS ≥ 120 msec, except right bundle branch block ; QTcF (QT corrected for heart rate using Fridericia's method) ≥ 480 msec, except right bundle branch block
* Has an active infection requiring systemic therapy.
* Infection with HIV or hepatitis B or C.
* Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix.
* Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment.
* Any gastrointestinal surgery that is likely impact upon the absorption of study treatment.
* Inability to tolerate oral medication.
* Unable to have blood drawn.
* Have had surgery within 28 days of the first dose of study medication.
* Prior use of strong/moderate CYP3A4 inhibitors or inducers within 28 days of the first dose of BMS-813160.
* Prior use of Class I antiarrhythmics within 28 days of first dose of study medication.
* Has ascites requiring medical management.
* Presence of duodenal or gastric invasion by the tumor.
* Hypersensitivity reaction to any monoclonal antibody.
* Known allergy or hypersensitivity to study drugs or any of their components of the study arm that participant is enrolling.
* Woman who are pregnant or breastfeeding.
* Patient is unwilling or unable to follow the study schedule for any reason.