Background: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinoma (GEA) patients and associated with poor prognosis. Recombinant mAbs to treat HER2/neu-amplified malignancies are effective with limitations so alternatives are needed. Therefore, we developed a B-cell epitope immunotherapy vaccine (IMU-131/HER-Vaxx) consisting of 3 fused B-cell epitopes (P467) from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This open-label multicenter Phase 1b study aimed to evaluate the optimal/safe IMU-131 dose leading to immunogenicity and clinical responses.Patients & Methods: Fourteen patients with HER2/neu overexpressing GEA were enrolled and dose escalation with 10, 30, and 50µg was performed in 3 cohorts. Immunogenicity was evaluated by P467- and HER2-specific Ab levels and cellular responses, and clinical response rates by CT/MRI scan evaluated according to RECISTv1.1. Results: IMU-131 was safe with no vaccine-related significant local or systemic reactions or SAEs. 11/14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete response, 5 showed partial response and 4 stable disease as their best response. HER2-specific IgG levels were dose-dependent. While in cohort 1 and 2 only 1/3 and 2/5 patients respectively responded with moderate to high Ab titers, all patients in cohort 3 mounted moderate to high HER2-specific IgGs. Additionally, cellular vaccine responses were induced, e. g. Th1-biased cytokine ratios and reduction of Tregs. The clinical response (progression free survival) was significantly prolonged in cohort 3 and showed a clear association with the magnitude of humoral and cellular vaccine responses. Conclusions: IMU-131 was well tolerated and safe. The vaccine-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 two arms, chemotherapy with IMU-131 vaccine or chemotherapy alone, which is currently ongoing. https://clinicaltrials.gov/ct2/show/NCT02795988

Citation Format: Marina Maglakelidze, Dinara Ryspayeva, Iurie Bulat, Zoran Andric, Ivan Nikolic, Tanuj Chawla, Rajnish Nagarkar, Vaibhav Chourdhary, Giri Venkata, Rajesh Kumar Singh, Davorin Radosavljevic, Zoran Petrovic, Ursula Wiedermann, Leslie Chong, Nicholas J. Ede, Rita Laeufle, Anthony Good. A PHASE 1B/2 OPEN-LABEL STUDY WITH RANDOMIZATION IN PHASE 2 OF IMU-131 HER2/NEU PEPTIDE VACCINE PLUS STANDARD OF CARE CHEMOTHERAPY IN PATIENTS WITH HER2/NEU OVEREXPRESSING METASTATIC OR ADVANCED ADENOCARCINOMA OF THE STOMACH OR GASTROESOPHAGEAL JUNCTION [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT107.