Abstract CT059: A Phase Ib open label multicenter study with a HER2/neu peptide vaccine administered with cisplatin and 5-fluorouracil or capecitabine chemotherapy shows safety, immunogenicity and clinical response in patients with HER2/Neu overexpressing advanced cancer of the stomach

Background: HER2/neu is overexpressed in 15-25% of gastric cancer patients and associated with poor prognosis. Alternative treatments to monoclonal antibodies are needed due to cost and global availability issues of mAbs. Thus a B-cell peptide vaccine (IMU-131) was developed, consisting of 3 fused B-cell epitopes (p467) from the HER2/neu extracellular domain coupled to CRM197 applied with the adjuvant Montanide. The current study evaluated the optimal and safe vaccine dose leading to immunogenicity and clinical responses. Material & Methods: In an open-label multicenter Phase Ib trial in SE-Asia and Eastern Europe, 14 patients with HER2/neu overexpressing (++/+++) gastric or gastroesophageal junction adenocarcinoma were recruited to receive 3 injections of IMU-131 (days 0, 14, 35) in combination with chemotherapy (CT) every 21 days. Dose escalation with 10 µg, 30 µg and 50 µg was performed in 3 cohorts. Safety, immunogenicity and clinical responses were evaluated. Results: No SAEs related to administration of IMU-131 were reported. Eleven of 14 patients were evaluable for vaccine-specific immune responses and 10 for tumor growth assessment. Higher p467- and Her-2 specific IgG levels were observed in cohort 2 (30 µg/dose) compared to cohort 1 (10 µg/dose). Two of five patients in cohort 2 showed minimal antibody titers. In contrast, all patients in cohort 3 (50µg/dose) responded to the vaccine with equally high antibody levels. Response rate was an exploratory endpoint and of 10 evaluable patients, 5 patients showed partial response and 4 patients showed stable disease. In cohort 3 the high antibody levels correlated with clinical response, while in cohort 2 only moderate correlations between humoral and clinical responses were observed. In cohort 1 partial response did not correlate with Ab levels, but rather with a high percentage of CD8 T-cells and increased inflammatory cytokine levels (high IFN-γ and TNF-α/IL-10 ratio). Conclusions: The vaccine was well tolerated and safe with antibody responses at the highest dose (50 µg) showing a strong correlation with clinical responses. Thus, a dose of 50 µg was recommended for further evaluation in Phase II, featuring two arms of either IMU 131 plus CT or CT alone. We propose that this vaccine might be of significant medical benefit and further trials are warranted. Citation Format: Ursula Wiedermann, Erika Garner-Spitzer, Yee Chao, Iurie Bulat, Arunee Dechaphunkul, Wichit Arpornwirat, Chaiyut Charoentum, Chia-J