Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

Inclusion Criteria: * 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 Criteria 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) …