Abstract #722: A HER2 multi-peptide virosome vaccine induced HER-2 specific antibodies in patients with metastatic breast cancer: final results of a phase I study to evaluate safety and immunogenicity

Background: We have shown previously that vaccination of rodents with three HER-2-peptides representing B-cell epitopes of the extracellular domain of HER-2 can induce HER-2-specific IgG production, which results in a delayed tumor onset and reduced tumor growth progression in c-neu transgenic mice. We have now concluded a phase I clinical trial with an anti-HER-2 vaccine-construct of immunopotentiating reconstituted influenza virosomes with the three peptides (PEV6A) in patients with metastatic breast cancer (MBC). Methods: 10 patients with MBC with low HER2 expressing tumors (+ or ++) and positive hormone receptors were enrolled in a single arm, single-centre study. The study endpoints were safety, and immunogenicity as measured by induction of peptide- and HER-2-specific antibodies, and anti-HER-2 specific T-cell responses. Patients received 3 intramuscular vaccinations in monthly intervals each consisting of PEV6A containing 10ug of each peptide. Results: Non of the 10 patients experienced a drug-related adverse events higher than grade 2. Local erythema at the injection site were the most frequent drug-related AEs. One patient died one month after the last vaccination due to disease progression. All the remaining 9 patients are alive, 5 are stable for a period of up to 12 months and 4 had disease progression after 5 to 11 months. In 9 of 10 patients an increase in peptide-specific antibody titers as measured by ELISA was found. Furthermore in 7 of these 9 patients the induced antibodies were also found to be HER-2 specific. Cellular immune response as measured by production of IFN-\#947;, TNF-\#945; and IL-2 in a culture of patients peripheral mononuclear cells after stimulation with virosomes showed an increase in all but one patient. Conclusions: PEV6A is safe, very well tolerated. The induction of anti-HER-2 specific antibodies could result in clinical benefit comparable to passive anti-HER-2 antibody therapy. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 722.