A phase 1b study of IMU-131 her2/neu peptide vaccine plus chemotherapy in patients with HER2/neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction

Abstract

Introduction: Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths. HER2/neu is overexpressed in 15%-25% of patients with gastric cancer. Monoclonal antibodies against HER2/neu are effective but alternatives are needed due to the cost and lack of availability globally. IMU-131 is a B-cell peptide vaccine composed of a fusion of 3 epitopes from the extracellular domain of HER2/neu conjugated to CRM197 with the adjuvant Montanide. Polyclonal antibodies against IMU-131 peptides elicit antitumor activity in vitro and a phase I study demonstrated safety and immunogenicity in Her-2 +/ ++ breast cancer patients. Methods: IMU-131 was given to patients with HER2/neu overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma in an international open-label Phase 1b dose-escalation trial performed in 14 Asian and Eastern European sites assessing safety, tolerability, and immunogenicity. Each patient received IMU-131 on Days 0, 14, and 35, accompanied by cisplatin and 5-fluorouracil or capecitabine every 21 days. Results: 14 patients were enrolled with advanced stage IIIb or IV with 10 HER2 overexpressing tumors (7 x HER2 +++, 3 x HER2 ++ FISH positive) and 4 HER2 ++ expressing tumors. Mean age was 57 yo (range of 21 - 79) with ECOG scores of 0 or 1 in 7 patients each. There were 9 Asian and 5 Caucasian patients with 5 females and 9 males. Dose levels were 0.1, 0.3 and 0.5 mg with 3, 6, and 5 patients receiving those dose levels, respectively. Eleven patients received all 3 doses, 3 patients received only 2 doses due to disease progression, and 2 patients received a dose on day 182. Of the 14 patients dosed, 11 were evaluable for tumor progression at day 56 and later. Of those patients, the best response was 1 CR, 4 PR, 5 SD, and 1 PD. In the 0.1 mg dose group, the best response was 1 CR and 2 SD, with 2 PR, 2 SD, and 1 PD in the 0.3 mg group, and 2 PR and 1 SD in the 0.5 mg group. In patients with HER2 overexpression, there was 1 CR, 4 PR, 2 SD, and 1 PD, and in patients with HER2 ++ expression, there was 3 SD. There were no SAEs related to IMU-131 and 1 patient had a mild injection site reaction. Conclusion: IMU-131 is a promising B-Cell vaccine against HER2. Further work in a controlled phase 2 trial is ongoing.