Neoantigen-Targeted Vaccine Combined With Anti-PD-1 Antibody for Patients With Stage IV MMR-p Colon and Pancreatic Ductal Cancer

Inclusion Criteria: * Age ≥18 years. * Have histologically or cytologically - proven cancer of the pancreas or colon. * Have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator). * Measurable disease as per RECIST 1.1. * Have sufficient and accessible tissue for NGS and immune-phenotyping. * Have not received any prior systemic therapy in the metastatic setting for PDA or CRC. Patients who have received adjuvant chemotherapy \>12 months prior to the diagnosis of metastatic disease may be eligible. * ECOG performance status 0. * Life expectancy of greater than 6 months. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug. * Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol. * Men must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: * Is a candidate for definitive surgical resection. * Is unwilling or unable to undergo standard of care therapy. * Known history or evidence of brain metastases and/or leptomeningeal spread. * Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.). * Receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days of vaccine treatment. * Has active autoimmune disease that has required systemic treatment in the past 5 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. * Known history or concurrent interstitial lung disease. * Has a pulse oximetry \< 95% on room air. * Requires the use of home oxygen. * Infection with HIV or hepatitis B or C. * Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements. * Has been diagnosed with another cancer or myeloproliferative disorder within the past 5 year. * Has had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement. * Has received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment. * If at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements. * Any other sound medical, psychiatric, and/or social reason as determined by the Investigator. * Unwilling or unable to follow the study schedule for any reason. * Are pregnant or breastfeeding. * Any radiological or clinical pleural effusions or ascites. * Any peritoneal involvement by the tumor. * History of malignant small bowel obstruction. * On parenteral nutrition. * Any liver metastasis greater than 3 cm or greater than 5 liver metastases. * Known or suspected hypersensitivity to Hiltonol.