Pepinemab with or without Ipilimumab or Nivolumab in Treating Patients with Stage I-III Pancreatic Cancer That Can Be Removed by Surgery or Stage IV Colorectal Cancer with Liver Metastasis That Can Be Removed by Surgery

Inclusion Criteria

• For patients with pancreatic cancer: * Stage I-III cytologically or histologically-proven pancreatic adenocarcinoma * Cancer confirmed to be surgically resectable, with surgery evaluation with planned resection * Patients may have prior neoadjuvant chemotherapy, but no neoadjuvant chemoradiation * No cancer chemotherapy treatment 2 weeks prior to day 2 of treatment
• For patients with metastatic colorectal cancer: * Stage IV histologically-proven colorectal adenocarcinoma * Liver metastasis confirmed to be surgically resectable, with surgery evaluation and planned resection; may have minimal extrahepatic disease that is determined to be resectable * Tumor must be confirmed to be microsatellite stable (MSS); if not already reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we will be able to perform this at Emory University * No prior immunotherapy * No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count >= 1,500 cells/uL
• Platelets >= 100,000/uL
• Hemoglobin >= 9.0 g/dL (may receive packed red blood cell [prbc] transfusion)
• Total bilirubin =< 1.5 x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Albumin >= 3.0 g/dL
• Serum creatinine =< 1.5 x ULN
• Calculated creatinine clearance of >= 50 mL/min
• International normalized ratio (INR) =< 1.5; anticoagulation is allowed only with low molecular weight heparin (LMWH); patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Ability to understand and willingness to sign a written informed consent document
• Female subjects of childbearing potential must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 3 months after completion
• Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for the duration of study treatment and 3 months after completion
• Female subjects of childbearing age must have a negative serum pregnancy test at study entry

Exclusion Criteria

• Poor venous access for study drug administration
• Determined not to be a surgical candidate due to medical co-morbidities
• Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
• Prior organ allograft or allogeneic bone marrow transplantation
• Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Women who are pregnant or lactating
• Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
• Clinical evidence of bleeding diathesis or coagulopathy
• Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years; patients with prior in situ carcinomas are eligible provided there was complete removal
• Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment
• Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
• History of severe hypersensitivity reactions to other monoclonal antibodies
• Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab