A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Breast Cancer After Adjuvant Therapy

Breast Cancer Clinical Trial

Official title: A Phase I Safety and Immunogenicity Trial of MVA-BN®-HER2 Vaccine in HER-2-Positive Breast Cancer Patients Following Adjuvant Therapy

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT01152398
• Study type: Interventional
• Source: Bavarian Nordic
• Status: Completed
• Phase: Phase 1
• Start date: June 2010
• Completion date: September 2012