A Phase I Safety and Immunogenicity Trial of MVA-BN®-HER2 Vaccine in HER-2-Positive Breast Cancer Patients Following Adjuvant Therapy
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
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
Patients will receive 6 subcutaneous vaccinations at 4-week intervals and will have blood
drawn for immune function analysis.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number and type of adverse events as a measure of safety and tolerability of multiple vaccinations
United States: Food and Drug Administration
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