HERIZON: A phase 1B/2 open-label study of imu-131 HER2/neu peptide vaccine PLUS standard of care chemotherapy with randomization in phase 2 in patients with HER2/neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction.

Abstract

e16065 Background: The phase 2 part of the study hypothesizes HER-Vaxx (IMU-131) will provide treatment benefits consistent with traditional monoclonal antibodies that target HER2 in patients with confirmed Her2+ advanced or metastatic gastric cancer with a corresponding adaptive immune response without added toxicity. In the phase 1b dose finding part of the study tumor response of patients who received 50ug dose strongly correlated with antibody levels with 50ug selected as the phase 2 dose (Wiedermann et. al., 2019). Phase 2 is a randomized two arm study of either HER-Vaxx plus standard chemotherapy or standard chemotherapy alone. The primary endpoint is overall survival, with progression-free survival, safety and immune related changes in humoral and cellular immunogenicity secondary endpoints. Methods: Patients received SOC chemotherapy for a maximum of 6 cycles with the HER-Vaxx group also receiving 50ug dose of IMU-131 at Baseline/Day 0, Day 14, Day 35, Day 77 and then every 63 days until disease progression. The per protocol pre-planned first interim analysis (OS, PFS and safety) in a total of 27 patients after 15 progression events was reviewed by the independent data monitoring committee (IDMC). Results: Within ITT analysis, 8 of 27 patients died on the control arm and 4 on the HER-Vaxx plus SOC chemotherapy arm with an overall survival HR of 0.418 (2 sided 80% CI: 0.186, 0.942) and a 1-sided p-value of 0.083. Out of 27 patients, 9 patients progressed on the control arm while 6 patients progressed on the HER-Vaxx plus SOC chemotherapy arm with a HR of 0.532 (2 sided 80% CI: 0.267, 1.060) and a 1-sided p-value of 0.086. A robust HER2 specific antibody response developed in the HER-Vaxx arm compared to the control arm whereas there was no difference in safety between the two treatment arms. Conclusions: The IDMC confirmed that the safety of the study was favorable with no added toxicity of HER-Vaxx and SOC chemotherapy with a favorable risk-benefit for the combination. The study has completed enrollment and final data is expected in late 2021. Clinical trial information: NCT02795988.