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NeuVax, (E75 plus granulocyte macrophage colony stimulating factor (GM-CSF)) is a peptide-based adjuvant immunotherapy aimed at reducing the recurrence of node positive breast cancer in low-to-intermediate HER2-positive breast cancer patients. It is being developed by Galena Biopharma and has entered Phase 3 clinical trials under an FDA approved Special Protocol Assessment (SPA). NeuVax stimulates the immune system by directing “killer” T-cells to target and destroy cancer cells that express HER2/neu, a protein associated with epithelial tumors in breast, ovarian, pancreatic, colon, bladder and prostate cancers.

About NeuVax
NeuVax is a peptide-based immunotherapy intended to reduce the recurrence of breast cancer in low-to-intermediate HER2-positive breast cancer patients not eligible for trastuzumab (Herceptin®; Genentech/Roche). NeuVax has been shown to be most effective in patients with low-to-intermediate HER2/neu expressors with HLA type A2+ or A3+. Approximately 25,000-40,000 of the approximately 200,000 women diagnosed with breast cancer in the United States each year meet these criteria.

NeuVax has two components: a HER2/neu-derived peptide called E75 and the immune adjuvant GM-CSF. E75 is a nine‑amino acid sequence that is immunogenic (produces an immune response); and GM-CSF is a commercially available protein that acts to stimulate and activate components of the immune system such as macrophages and dendritic cells.

NeuVax PRESENT study
On January 20, 2012, the PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) trial for NeuVax was initiated in HER2 1+ and 2+ breast cancer patients (often referred to as HER2 negative) in the adjuvant setting to prevent recurrence. The PRESENT study is a randomized, multicenter, multinational clinical trial that will enroll approximately 700 breast cancer patients. The trial design has been updated to include current National Comprehensive Cancer Network (NCCN) guidelines and has received Special Protocol Assessment (SPA) concurrence from the U.S. Food and Drug Administration (FDA). Based on a previous Phase 2 trial of NeuVax that achieved its primary endpoint of disease-free survival (DFS) the FDA has agreed in the SPA that the design and planned analysis of the Phase 3 PRESENT study is adequately designed to provide the necessary data that, depending upon the outcome, could support a regulatory submission for marketing approval. A Phase 2 trial was reported in which none (0%) of the Phase 3 targeted low-to-intermediate, node positive patients treated with the optimal regimen relapsed at the 36 month period compared to a recurrence rate of 22% in the placebo arm.

NeuVax (E75) combined with Herceptin (trastuzumab)
Preclinical studies and pilot Phase 2 clinical trials suggested that combining NeuVax and trastuzumab (Herceptin; Genentech/Roche) can increase antigen presentation by tumor cells by promoting receptor internalization and subsequent proteosomal degradation of the HER2 protein. Based on these results, a randomized, multicenter Phase 2 trial with 300 patients will compare NeuVax with trastuzumab versus trastuzumab alone.

A previous pilot Phase 2 trial investigated sequential therapy with trastuzumab followed by HER2 vaccination in the adjuvant setting. Of 62 patients who received standard-of-care trastuzumab, the 32 who received no vaccine experienced a 12.5% breast cancer recurrence rate (4/32), comparable with reported rates of similarly staged and treated patients. In contrast, of the 30 patients who were treated with vaccine following trastuzumab therapy, the recurrence rate was 0% (0/30).