First-In-Human Phase I Study Of Bvac-B Cell Therapy In Her2-Positive Advanced Gastric Cancer.

4534 Background: BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HER2/neu gene and loaded with alpha-galactosyl ceramide, a natural killer T cell ligand. It may have activity against HER2/neu positive cancer. Preclinical data in mouse models have shown promising anti-tumor activity by eliciting broad spectrum of immune responses against HER2/neu positive tumor cells. We report here the results of phase 1 study of BVAC-B in HER2 positive advanced gastric cancer. Methods: Metastatic gastric cancer with IHC > 1+ of HER2/neu were eligible for enrollment. Two weeks before treatment, subjects were admitted to hospital for collection of PBMC and plasma by lymphapheresis. The PBMC were sent to Cellid for vaccine manufacturing which took a day. BVAC-B was given intravenously at 0, 4, 8, and 12 weeks. Subjects received low (2.5X 107 cells/dose), medium (5.0X 107 cells/dose) or high dose (1.0X 108 cells/dose). Endpoints included safety, tolerability and MTD for phase 2 trial. Exploratory outcomes included immune responses after BVAC-B administration. Results: As of January 29, 2020, 8 subjects were treated with BVAC-B at doses of 2.5X 107 cells/dose (n=1), 5.0X 107 cells/dose (n=1) and 1.0X 108 cells/dose (n=6). Median line of therapy at which BVAC-B was administered was 4 (range, 2-9). Mean duration treatment was 1.8 (range 1-4) cycles. The most common treatment related adverse events were fever (n=4, 50%). One subject enrolled in medium dose experienced cytokine release syndrome (G2) with high fever (39.3℃) and hypotension 8 hours after first administration, but was manageable with hydration and supportive management. Other adverse events included increase of AST and ALT (G1, n=1 and G2, n=2), and hypotension (G1, n=1). There were no adverse events which led to treatment discontinuation. Immunologic response analysis showed that BVAC-B induced activation of natural killer T cells, natural killer cells, HER2/neu specific T cells, and release of HER2/neu specific antibody upon vaccinations in few patients who were evaluated. Conclusions: BVAC B is feasible and has acceptable toxicity profile. We considered all dose evaluated in this study available for phase 2 study, given that the maximum tolerated dose is expected to exceed the maximum dose administered in this study. For clinically relevant effect, further studies are warranted, including earlier line of exposure to BVAC-B as well as combination treatments. Clinical trial information: NCT03425773 .