Zimberelimab and Quemliclustat in Combination With Chemotherapy for the Treatment of Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

Inclusion Criteria: * Male or female \>= 18 years of age and willing and able to provide informed consent * Previously untreated cytologically or histologically confirmed pancreatic adenocarcinoma with one of the following: * Borderline resectable disease. There are multiple definitions of borderline resectable PDAC including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on CT; * An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring \>= 180 degrees of the circumference of the vessel wall * Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction * Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction * An interface between the tumor and SMA measuring \< 180 degrees of the circumference of the vessel wall * Locally advanced disease. Multiple guidelines defining locally advanced PDAC have been developed, including the MD Anderson definition, the National Comprehensive Cancer Network (NCCN) definition, as well as the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT; * Occlusion of the SMV-PV that is not amenable to resection and venous reconstruction * Interface between tumor and hepatic artery that is not amenable to resection and reconstruction * Interface between the tumor and SMA measuring \> 180 degrees of the circumference of the vessel wall * Interface between the tumor and celiac axis measuring \> 180 degrees of the circumference of the vessel wall * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelets \>= 100 x 10\^9/L * Hemoglobin \>= 9 g/dL * Serum creatinine (sCr) =\< 1.5 x upper limit of normal (ULN) or Creatinine clearance (Ccr) \>= 40 mL/min (as calculated by Modified Cockcroft-Gault formula) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (AST/\[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN * Women with no childbearing potential because of surgery or who are at least 1 year postmenopausal (ie, 12 months post last menstrual period) or with menopause confirmed by follicle-stimulating hormone testing * Women of childbearing potential must use an effective nonhormonal method of contraception (intrauterine device or intrauterine system; condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; or vasectomized male partner if he is the sole partner of that participant) for the duration of the study and for up to 6 months after the last dose of zimberelimab or quemliclustat * Male participants must use an effective method of contraception (condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository, or vasectomy) throughout the study and for up to 6 months after the last dose of zimberelimab or quemliclustat * Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before study treatment administration. Physiologic doses of corticosteroids (=\< 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (=\< 3 days) may be permitted * Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before study treatment administration. Participants should have recovered from the surgical procedure prior to the first dose being administered Exclusion Criteria: * Recurrent or metastatic pancreatic adenocarcinoma * Peripheral neuropathy \> grade 2 * Known status of human immunodeficiency virus (HIV) which is not well-controlled (CD4 \<300) at the time of study eligibility. Patients with controlled and treated HIV/Hepatitis C virus (HCV) and an undetectable viral load are allowed * Untreated Hepatitis B infection: Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) infection (testing is not mandatory, unless required by local regulation) * Participants with resolved or treated HCV (ie, HCV antibody positive but undetectable HCV ribonucleic acid \[RNA\]) will not be excluded from this study * Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of Investigational products (IPs) hazardous, including but not limited to: * Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis (lymphangitic spread of non-small cell lung cancer (NSCLC) is not disqualifying) * Active viral, bacterial, or fungal infections requiring parenteral