neoantigen-targeted vaccine combined with anti-pd-1 antibody for patients with stage iv mmr-p colon and pancreatic ductal cancer

Conditions: Pancreatic Cancer Metastatic; Colorectal Cancer Metastatic

Summary: phase 1 study evaluating feasibility, safety, and immune response to a personalized neoantigen vaccine combined with retifanlimab for mmr-p mcrc and mpdac patients with measurable disease following first-line folfirinox/folfoxiri (ffx).


Eligibility criteria:
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.

Keywords: neoantigen vaccines anti-pd-1 retifanlimab cancer vaccines immunotherapy colon cancer metastatic colon cancer pancreatic ductal adenocarcinoma (pdac) metastatic pancreatic cancer