Modified
vaccinia Ankara (MVA) encoding the
tumor antigen 5T4 (
TroVax) has been evaluated in an open label phase II study in metastatic
colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of
TroVax injected before, during and
after treatment with
5-fluorouracil,
leukovorin and
irinotecan.
TroVax was administered to 19 patients with metastatic
colorectal cancer. Twelve patients had blood samples taken following each of the six
injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the
tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of
TroVax alongside
chemotherapy was safe and well tolerated with no SAEs attributed to the
vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to > 5,000. IFNgamma ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during
chemotherapy and four had CEA levels which remained stable for > 1 month following completion of
chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which
chemotherapy was administered. These data demonstrate that
TroVax can be layered on top of
chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy.