GUCY2C Prime-Boost Vaccination for Advanced Colorectal and Small Bowel Adenocarcinomas

This phase 1 study is an open-label study of heterologous prime-boost vaccination with Ad5.F35-hGUCY2C-PADRE and recombinant listeria monocytogenes (Lm-GUCY2C) vaccines in patients with advanced solid tumors including colorectal cancer and small bowel adenocarcinomas who have progressed on available standard therapies.. Subjects will receive Ad5.F35-hGUCY2C-PADRE intramuscularly (IM) followed by two administrations of the Lm-GUCY2C vaccine intravenously (IV) as described and will be followed primarily to evaluate safety endpoints for the duration of the study (through eight weeks after the first administration of Lm-GUCY2C). The main objective of this Phase I trial is to determine the MTD and the RPTD of this prime-boost vaccination regimen. Subjects will be enrolled by Bayesian optimal interval (BOIN) design in dose-escalation cohorts of three. The first cohort will receive Lm-GUCY2C at a dose of 3 x 10⁸ CFU, and this dose will be escalated to subsequent levels (1 x 10⁹, 3 x 10⁹ CFU) with each cohort according to the BOIN model until the maximum dose, barring excessive rates of dose-limiting toxicities. One dose level will be reserved for de-escalation if necessary (1 x 10⁸ CFU). Subjects will receive treatment over a 12-week period including the Ad5.F35-hGUCY2C-PADRE vaccine, with evaluation of DLTs over 4 weeks following the first Lm-GUCY2C vaccine and clinical and laboratory monitoring after the second Lm-GUCY2C vaccine. Only the necessary safety evaluations will be conducted after Ad5.F35-hGUCY2C-PADRE vaccination. Subjects will be actively followed (clinical and laboratory evaluations) for 12 weeks following first vaccination with Ad5.F35-hGUCY2C-PADRE. Then, they will be followed every 3 months for Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. evaluation until all subjects have had disease progression or have started new anti-cancer therapies or death.