The purpose of this research study is to learn more about a new combination of drugs being given to treat pancreatic cancer. The drugs being tested are BMS-813160, nivolumab, gemcitabine, and nab-paclitaxel. The investigators will be looking at both the side effects and the way the disease responds to treatment.

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or borderline resectable pancreatic ductal adenocarcinoma. Patients with clinical suspicion of pancreatic adenocarcinoma can be enrolled for pre-treatment biopsy, and must be histologically confirmed to have adenocarcinoma before being treated on study. Patients with squamous carcinoma, adenosquamous carcinoma or neuroendocrine tumor will be excluded. Tumor Biopsy can be omitted, if deemed by PI and treatment physician, that it may incur immediate, excessive health risks to patients. This determination (rationale and discussion with PI and treating physician) should be clearly documented in the screening visit notes.

• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI.

• At least 18 years of age.

• ECOG performance status ≤ 1

• Normal bone marrow and organ function as defined below:

  • Leukocytes ≥ 2,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcl
  • Hemoglobin ≥ 8.5 g/dL
  • Platelets ≥ 100,000/mcl
  • Total bilirubin ≤ 1.5 x IULN (except participants with Gilbert's Syndrome who must have normal direct bilirubin)
  • AST(SGOT)/ALT(SGPT) ≤ 3 x IULN
  • Serum albumin ≥ 3g/dL
  • Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 40 mL/min by Cockcroft-Gault for patients with creatinine levels above institutional normal

• Women of childbearing potential and men must agree to use at least two forms of contraception (hormonal, barrier method of birth control, abstinence, and must include barrier method) prior to study entry, for the duration of study participation, and through 5 months (for women) or 7 months (for men) after the last dose of treatment on this study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Able to understand and willing to sign an IRB approved written informed consent document.

• All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) or baseline before administration of study treatment. Participants with toxicities attributed to prior anti-cancer therapy that are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enroll.

Exclusion Criteria:

• Prior exposure to chemotherapy or radiation for the disease to be treated on this trial not allowed.
• Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric, colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period. Other active malignancy requiring concurrent intervention
• Currently receiving any other investigational agents, or exposure to any investigational drug or placebo within 4 weeks of study treatment
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BMS-813160, nivolumab, gemcitabine, paclitaxel, nab-paclitaxel, or other agents used in the study.
• Prior exposure to anti-PD-1, anti-PD-L1, CCR2/5, or anti-CTLA4 antibodies.
• Taking immunomodulatory agents (including steroids and NSAIDs). A wash-out period of at least 4 weeks or 5 half-lives, whichever is shorter, is required for patients receiving immunomodulatory agents at the time of enrollment.

Note: daily use of low dose aspirin (e.g. 81 mg PO QD) is not considered an immunomodulatory agent and patients are still eligible for enrollment despite taking such medication at a low dose

• Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussing with the Principal Investigator

• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study treatment except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted.

• History of allogeneic organ or stem cell transplant.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry and again within 24 hours prior to first treatment.

• Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (by PCR).

• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Anti-retroviral agents are known to have potential adverse pharmacokinetic interactions with nivolumab and/or BMS-813160. IN addition, patients not on anti-retroviral agents, regardless of HIV viral load, are at increased risk of lethal infections with marrow-suppressive therapy including chemotherapy. Testing for HIV must be performed at sites mandated by local requirements.

• Requires continued use of warfarin for anticoagulation and cannot stop warfarin or be safely switched to another anticoagulant.

• Current or recent (within 3 months of study treatment administration) gastrointestinal disease or conditions that could interfere with the swallowing or absorption of study medication or inability to tolerate oral medication.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to administration of study medication; immunosuppression; autoimmune conditions; underlying pulmonary disease; or psychiatric illness/social situations that would limit compliance with study requirements.

• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.

• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:

  • Myocardial infarction or stroke/transient ischemic attack within the past 6 months
  • Uncontrolled angina within the past 3 months
  • Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
  • QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation > 480 msec
  • History of other clinically significant heart disease (e.g. cardiomyopathy, congestive heart failure with NYHA functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis)

• Major surgery within 28 days prior to the first study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.

• Concurrent use of oral or intravenous medications or food which may interfere with BMS-813160 including any strong inhibitors or inducers of CYP3A4 or P-gp is not allowed. These include but are not limited to Class I antiarrhythmics (eg, quinidine, procainamide, dysopiramide, lidocaine, phenytoin, mexiletine, tocainide, flecainide, propafenone, moricizine), Grapefruit and Seville oranges.