Patient description: The patient is a 57-year-old man with abdominal pain and vomiting. The pain started gradually about 20 hours ago in the epigastric and periumbilical regions, radiating to his back. He drinks around 60 units of alcohol per week and smokes 22 cigarettes per day. He is healthy with no history of allergies or using any medications. His family history is positive for type 2 diabetes (his father and sister). He lives alone and has no children. The abdomen is tender and soft. His bowel sounds are normal. His heart rate is 115/min and blood pressure 110/75 mmHg. The lab results are remarkable for leukocytosis (19.5), urea of 8.5, high CRP (145), high amylase (1200) and Glc level of 15. Cross-sectional imaging was negative for obstructive pancreatitis.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Colorectal Adenocarcinoma Metastatic Pancreatic Adenocarcinoma Recurrent Colorectal Carcinoma Recurrent Pancreatic Carcinoma Stage III Colorectal Cancer Stage III Pancreatic Cancer Stage IIIA Colorectal Cancer Stage IIIB Colorectal Cancer Stage IV Colorectal Cancer Stage IV Pancreatic Cancer Stage IVA Colorectal Cancer Stage IVA Pancreatic Cancer Stage IVB Colorectal Cancer Stage IVB Pancreatic Cancer Unresectable Pancreatic Carcinoma Patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, gastroesophageal junction [GEJ], cholangiocarcinoma, hepatocellular, pancreas, colorectal, small intestinal tumors) who have failed at least one prior therapy (dose escalation phase) Patients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen; eight patients must have tumors that are accessible for biopsy and sign the informed consent for paired biopsy study (dose escalation phase, arm A) Patients with colorectal adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and fluoropyrimidine; eight patients must have tumors that are accessible for biopsy and sign the informed consent for paired biopsy study (dose escalation phase, arm B) Be willing and able to provide written informed consent/assent for the trial Have measurable disease based on Response Evaluation in Solid Tumors (RECIST) 1.1 Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale Absolute neutrophil count (ANC) ≥ 1,500 cells/µL Platelets ≥ 100,000 cells/µL Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN  Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment Has a known history of active tuberculosis (TB) (Bacillus tuberculosis) Hypersensitivity to pembrolizumab or history of severe allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol [PEG] 300 and polysorbate 80) Clinically significant cardiovascular disease or peripheral vascular (e.g. myocardial infarction, unstable angina within 6 months of study entry), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia requiring medications, baseline corrected QT (QTc) > 450 msec or previous history of QT prolongation while taking other medications 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 Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent Note: Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy