BMS-813160 With Nivolumab and Gemcitabine and Nab-paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

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 requi