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

Abstract Background HER2/neu is overexpressed in 15% - 25% of gastric cancers. IMU-131 is a B-cell peptide vaccine composed of 3 epitopes of the extracellular domain of HER2/neu. Antibodies against IMU-131 peptides elicit antitumor activity in vitro and a phase I study demonstrated safety and immunogenicity in Her-2 +/\u2009++ breast cancer patients. Methods IMU-131 was given to patients with HER2/neu positive gastric cancer in an open-label phase 1b dose escalation trial with 14 Asian and Eastern European sites. Each patient received IMU-131 on Days 0, 14, and 35, with cisplatin and 5-fluorouracil or capecitabine every 21 days. Patients remained on study until disease progression. Ongoing patients received boosters at D98 then every 84 days. Results 14 patients were enrolled with 10 HER2 overexpressing (7 x HER2\u2009+++, 3 x HER2\u2009++ FISH positive) and 4 HER2\u2009++ 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 10, 30 and 50 µg with 3, 6, and 5 patients respectively. 11 patients received all 3 doses and 3 patients received only 2 doses due to disease progression. P467 and HER2 antibodies were generated at all dose levels with patients dosed at 50µg responding to the vaccine with equally high antibody levels. There were no DLTs or SAEs related to IMU-131. 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, 5 PR, 4 SD and 1 PD. Two patients, both dosed at 50µg IMU-131, remain on study after D266, with one patient’s tumor reduced by approximately 80% from 177mm at baseline to 37mm at D266. Conclusions Safety data indicate that IMU-131 is well tolerated with no significant local or systemic reactions. There were no dose-limiting toxicities observed, no significant injection site reactions and no IMU-131 related SAEs. The 50µg dose produced the most consistent P467 and HER-2 specific antibodies compared to 10 and 30µg doses with preliminary response data demonstrating 50µg of IMU-131 is associated with tumor size reduction. The 50µg dose of IMU-131 is being used in the phase 2 study. Clinical trial identification Identifier: NCT02795988. Legal entity responsible for the study Imugene Ltd. Funding Imugene Ltd. Disclosure N. Ede: Full / Part-time employment: Imugene. L. Chong: Full / Part-time employment, Officer / Board of Directors: Imugene. A. Good: Full / Part-time employment: Imugene. All other authors have declared no conflicts of interest.