The current trial, BNIT-BR-003, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2 following adjuvant chemotherapy in patients with HER-2-positive breast cancer. The intent of vaccination is to induce a combined antibody and T-cell anti-HER-2 immune response, which is intended to target HER-2-expressing tumor cells, and may induce tumor regression or slow progression of disease.
MVA-BN®-HER2 is a candidate breast cancer immunotherapy product comprised of a highly attenuated non-replicating vaccinia virus, MVA-BN®, engineered to encode a modified form of the HER-2 protein. MVA-BN® is a well-characterized, clonal strain of modified vaccinia virus Ankara (MVA) being developed as a smallpox vaccine, suitable for use in high-risk (e.g., immunocompromised) individuals. MVA-BN®-derived vectors encoding heterologous antigens are being developed for use as vaccines for infectious diseases such as HIV, and for the treatment of cancer. A large database exists from safety evaluations in animals and in humans for MVA-BN®, and MVA-BN®-derived vectors. HER-2 is overexpressed in 20-30% of human breast cancers. It is an oncogene/growth factor receptor critical for the malignant phenotype of HER-2- expressing tumors. It is an immunogenic target, and immune responses to this protein have been shown to mediate potent anti-tumor activity in multiple animal models. Means to stimulate anti-HER-2 reactivity are now being studied clinically. Sponsor, collaborators, and others have used both Protein and DNA vaccine forms of HER-2, and a safety database is developed and no significant adverse events have resulted from HER-2 directed vaccination. MVA-BN®-HER2 encodes a modified form of the HER-2 protein, hereinafter referred to as HER2. HER2 contains the extracellular domain of HER-2 but lacks the intracellular, cell signaling domain. In addition, HER2 includes two universal T-cell epitopes from tetanus toxin to facilitate the stimulation of an immune response to HER-2, a self-protein. The current trial, BNIT-BR-003, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2 following adjuvant chemotherapy in patients with breast cancers which overexpress HER-2. Patients will receive 6 subcutaneous vaccinations at 4-week intervals and will have blood drawn for immune function analysis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
experimental vaccine, subcutaneous injection q4weeks x6
Alta Bates Comprehensive Cancer Center
Berkeley, California, United States
Number and type of adverse events as a measure of safety and tolerability of multiple vaccinations
Time frame: 18 months
Type and duration of immune response measured over time to repeat vaccine administrations
Time frame: 18 months
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