A Phase I Trial of a Fixed Dose of MVA-BN-HER2 Following 1st- or 2nd-Line Chemotherapy for HER-2-Positive Metastatic Breast Cancer
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 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-002, will evaluate the safety and biological activity of a fixed
dose of MVA-BN®-HER2, with and without Herceptin, following 1st- or 2nd-line chemotherapy in
patients with metastatic breast cancers which overexpress Her-2.
Patients will receive 3 subcutaneous vaccinations at 3 week intervals and have tumor
followed by CT/MRI imaging and blood drawn for immune function analysis.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability
2years, 3 months
United States: Food and Drug Administration
|Stanford Cancer Center||Stanford, California 94305-5824|
|Alta Bates Herrick Hospital Comprehensive Cancer Center||Berkeley, California 94705|