Clinical and immunologic responses to a B-cell epitope vaccine in HER2/neu overexpressing advanced gastric cancer patients - results from Phase 1b trial IMU.ACS.001

Background: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of 3 fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This Phase 1b study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses. Patients & Methods: 14 patients with HER2/neu-overexpressing GEA were enrolled and dose escalation (10, 30, 50μg) was performed in 3 cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECISTv1.1. Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or SAEs. 11/14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses and 4 stable diseases as their best response. HER2-specific IgG levels were dose-dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. Additionally, cellular vaccine responses such as Th1-biased cytokine ratios and reduced Treg numbers were generated. Progression free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses. Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose-dependent and correlated with clinical responses. The highest dose (50 µg) was recommended for further evaluation in a Phase II trial, with chemotherapy +IMU-131 or chemotherapy alone, which is currently ongoing.