MVA-5T4 immunotherapy and low-dose cyclophosphamide for advanced colorectal cancer (TaCTiCC): An open-label, randomized phase I/II trial.

154Background: Current immunotherapies including checkpoint inhibitors and vaccines for advanced colorectal cancer (CRC) have been largely ineffective. We hypothesized that combining an MVA-based vaccine targeting the tumor-associated antigen 5T4 ( TroVax) with low-dose cyclophosphamideto deplete Foxp3+ regulatory T-cells(Tregs), could improve immunological responses and patient outcomes. Methods: In this open-label phase I/II clinical trial, TaCTiCC ( TroVaxand CyclophosphamideTreatment in Colorectal Cancer) 53 patients with inoperable metastatic CRC were randomized to receive either no treatment (group 1, n=8), metronomiclow-dose CPM (50mg B.D. during treatment weeks 1&3; group 2, n=9), TroVaxonly (6 i.m. injections weeks 4 to 16, group 3, n=18), or low-dose CPM followed by TroVax(group 4, n=18). The primary endpoint was boosted anti-5T4 responses at week 7, as measured by increased T-cell and antibody responses; secondary endpoints included progression-free (PFS)/overall survival (OS), and anti-5T4...