Perioperative Mvt-5873, A Fully Human Monoclonal Antibody Against A Ca 19-9 Epitope, For Operable Ca 19-9 Producing Pancreatic Cancers, Cholangiocarcinomas, And Metastatic Colorectal Cancers.

TPS4655 Background: Operable hepatopancreatobiliary (HPB) cancers continue to pose significant challenges. Radical resections are rarely curative, and chemotherapy is able to reduce tumor recurrence for only a fraction of patients. Despite the obvious advantages of extirpation of the identifiable tumor(s), the inflammatory milieu that accompanies surgery and the obligate time off cytotoxic agents allows for activation of remote quiescent disseminated tumor cells, leading to metastatic recurrence. We are conducting a study to determine the safety and efficacy of immediate peri-operative MVT-5873, a cytotoxic monoclonal antibody targeting Carbohydrate Antigen 19-9 (CA 19-9), in patients undergoing resections pancreatic cancer, cholangiocarcinoma or metastatic colorectal cancer to the liver. MVT-5873 is a human IgG1 antibody isolated from a patient following immunization with a sLea-KLH vaccine. MVT-5873 has demonstrated cell surface binding in sLea positive human tumor lines and has been shown to be potent in complement-dependent cytotoxicity assays and antibody-dependent cell mediated cytotoxicity assays. In patients with CA 19-9-producing cancers, MVT-5873 treatment has been shown to decrease serum CA 19-9 levels and prevent tumor progression. This trial may open the door for investigation of additional and/or synergistic agents in the immediate peri-operative period and usher in a new paradigm in the management of surgically treated cancers. Methods: This is a prospective, Phase II trial designed to determine the efficacy (increase in 1-yr DFS) and safety of peri-operative MVT-5873 for subjects with operable pancreatic, liver and bile duct cancers with elevated CA 19-9 levels. Patients may receive any standard neoadjuvant regimen prior to enrollment at the NIH Clinical Center in Bethesda, Maryland. Eligible patients will receive a pre-operative dose of MVT-5873 three days prior to the planned operation to remove all demonstrable disease. Following the operation, patients will receive a total of four doses of MVT-5873; the first two doses on postoperative days four and ten. The third dose will be administered on the normally scheduled postoperative clinic visit, followed by a final dose one month after discharge from the hospital and prior to the start of adjuvant treatment. Clinical trial information: NCT03801915 .