First-in-Human Phase 1 Study of a B Cell- and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer.

Purpose BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. Materials and Methods Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. Results Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. Conclusion BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy. [ABSTRACT FROM AUTHOR]