Galena Biopharma, Inc., has announced that, on the recommendation from an independent data monitoring committee (IDMC), the phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer With Low to Intermediate HER2 Expression With NeuVax Treatment) trial has been stopped because of futility. The study was evaluating the efficacy of nelipepimut-S (NeuVax) in preventing breast cancer recurrence.
The planned safety and futility interim analysis was triggered after 70 qualifying disease-free survival (DFS) events were reached, and a total of 71 events were reviewed by the IDMC.
The PRESENT trial evaluated nelipepimut-S plus granulocyte macrophage-colony stimulating factor (GM-CSF) versus placebo plus GM-CSF in breast cancer patients who were node-positive, human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+/2+, and human leukocyte antigen (HLA) A2+ and/or A3+. The study was double blind, randomized, and stratified by stage, type of surgery, hormone receptor status, and menopausal status. A total of 758 patients were enrolled, and the primary endpoint was disease-free survival upon reaching 141 events, with a minimum follow-up period of three years.
Nelipepimut-S is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard-of-care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) after binding to specific HLA molecules on antigen-presenting cells. These activated specific CTLs recognize, neutralize, and destroy, through cell lysis, HER2-expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, nelipepimut-S was combined with GM-CSF.
In addition to the PRESENT trial, Galena has two breast cancer studies ongoing with nelipepimut-S in combination with trastuzumab (Herceptin, Genentech/Roche): a phase 2b trial in node-positive and triple-negative HER2 IHC 1+/2+, and a phase 2 trial in high-risk, node-positive or node-negative HER2 IHC 3+ patients. Phase 2 clinical studies of nelipepimut-S are also planned in patients with ductal carcinoma in situ, and in patients with gastric cancer.
Source: Galena Biopharma; June 30, 2016.