The purpose of this study is to see if the combination of nivolumab + cabiralizumab + gemcitabine can give prolonged disease control in patients with advanced pancreatic cancer compared to gemcitabine alone.

The purpose of this study is to see if the combination of nivolumab + cabiralizumab + gemcitabine can give prolonged disease control in patients with advanced pancreatic cancer compared to gemcitabine alone.

Cabiralizumab is an antibody (a type of protein) that binds to a molecule called CSF-1r. CSF-1r is a molecule present on different types of cells in your immune system that controls parts of your immune system. Blocking CSF-lr could potentially stop the cancer cells which it appears on from escaping the immune system, which could then act to kill the cancer cells.

Nivolumab is an anti-PD-1 antibody that boost the body's immune system. It works by attaching to and blocking a molecule on white blood cells called PD-1. PD-1 is a protein that is present on different types of cells in your immune system and controls parts of your immune system by shutting it down. Antibodies that block PD-1 can potentially prevent PD-1 from shutting down the immune system, thus allowing immune cells to recognize and destroy cancer cells.

Gemcitabine is currently used to treat advanced or metastasized (spread) pancreatic cancer. It is used in patients whose disease cannot be removed by surgery and who have already been treated with other chemotherapy

Inclusion Criteria:

• Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis
• Must be off their prior cytotoxic regimen a minimum of two weeks but no more than four weeks from initiating trial treatment.

Measurable disease by RECIST 1.1.

Demonstrate adequate organ function

Normal Vitamin D level.

Able to submit an archival tumor specimen (primary or metastatic site). Patients with cytology only that do not have adequate archived tumor specimen available, will require a baseline biopsy.

Exclusion Criteria:

• Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 3 weeks of the first dose of trial treatment.
• Hypersensitivity to cabiralizumab, nivolumab, or gemcitabine or any of its excipients.
• Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric, colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period.
• Evidence of central nervous system (CNS) metastasis
• Participants with active, known, or suspected autoimmune disease.
• Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels.
• Uncontrolled or significant cardiovascular disease
• Prior organ allograft or allogeneic bone marrow transplantation.
• Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis.
• Evidence of coagulopathy or bleeding diathesis.
• Has received prior therapy with a CSF-1R pathway inhibitors, anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4.

Through study completion (3 years & 8 months; 44 months)