A Multicenter Phase Ii, Open-Label Trial Of Multiple Doses Of Cancer Vaccine Candidate Ign101 To Evaluate Efficacy Against Disseminated Tumor Cells In Blood.

2557 Background: IGN101 is a vaccine designed for therapeutic immunization against cancers of epithelial origin. It consists of 0.5 mg alum-adsorbed murine monoclonal antibody 17-1A as vaccine antigen to trigger an immune response which has been shown in a phase I study with 18 patients to significantly reduce the number of circulating EpCAM-positive tumor cells in peripheral blood. Methods: An open-label, single treatment arm, uncontrolled study with at least 45 evaluable patients in at least four centers is being conducted. Patients are male or female, ≥18 years of age, with biopsy proven carcinoma likely to express EpCAM, with a Karnofsky Performance Score ≥70 at baseline and a life expectancy > 4 months. Vaccinations with IGN101 are given by subcutaneous injection on days 1, 15, 29 and 57. Analyses of circulating tumor cells (EpCAM-positive, cytokeratin-positive, CD45-negative) in peripheral blood are performed for screening of patients and on days 1, 29, 57 and 71 (study end) utilizing the method described by Cristofanilli et al., NEJM (2004) 351:781. Primary objective is to assess the effect of IGN101 on the number of circulating tumor cells in peripheral blood. Secondary objectives are safety and tolerability of multiple injections of IGN101 and to obtain data for several immunological parameters. Results: 16 patients have completed the study until November 2004, the median number of circulating tumor cells has been reduced from 10.5 at day 1 to 5 cells per blood sample after 4 vaccinations at day 71. This difference is not yet statistically significant. Conclusions: In a number of patients with colorectal, ovarian and breast cancer a reduction of circulating tumor cells is being observed after conclusion of approximately one third of the study. It has been shown that in metastatic breast cancer patients an elevated number of circulating tumor cells predicts short survival (Hayes et al., J. Clin. Oncol., ASCO Annual Meeting Proceedings (2004) 22: 509). This parameter could potentially be used to probe for surrogate efficacy in patients at an early stage of development of immunotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration igeneon AG igeneon igeneon AG igeneon AG