A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2-overexpressing tumors

• DOI: 10.1007/s10549-016-3751-x
• Publication Date: 2016-03-18T15:00:51Z
• Authors: Steven A. Limentani; Mario Campone; Thierry Dorval; Giuseppe Curigliano; Richard de Boer; Charles Vogel; Shane White; Thomas Bachelot; Jean-Luc Canon; Mary Disis; Ahmad Awada; Martine Berlière; Frédéric Amant; Ellis Levine; Wivine Burny; Andrea Callegaro; Pedro Miguel de S...; Jamila Louahed; Vincent Brichard; Frédéric F. Lehmann
• Keywords: Adult; Receptor, ErbB-2; Breast Neoplasms; Drug Administration Schedule; 03 medical and health sciences; 0302 clinical medicine; Humans; Immunologic Factors; Drug Dosage Calculations; DHER2 protein; Aged; Dose-Response Relationship, Drug; Cancer immunotherapeutic; HER2-overexpressing breast cancer; Middle Aged; Survival Analysis; Recombinant Proteins; Up-Regulation; 3. Good health; Cancérologie; Gene Expression Regulation, Neoplastic; Cancer immunotherapeutic; DHER2 protein; HER2-overexpressing breast cancer; Vaccine; Oncology; Cancer Research; Treatment Outcome; Female; Immunotherapy; Vaccine

This Phase I dose-escalation study (NCT00058526) assessed the safety and immunogenicity of an anti-cancer immunotherapeutic (recombinant HER2 protein (dHER2) combined with the immunostimulant AS15) in patients with early-stage HER2-overexpressing breast cancer (BC). Sixty-one trastuzumab-naive patients with stage II-III HER2-positive BC received the dHER2 immunotherapeutic after surgical resection and adjuvant therapy. They were allocated into four cohorts receiving different doses of dHER2 (20, 100, 500 µg) combined with a fixed AS15 dose. Safety and immunogenicity (dHER2-specific antibody responses) were assessed. After completing the immunization schedule (three or six doses over 14 weeks) and a six-month follow-up, the patients were followed for 5 years for late toxicity, long-term immunogenicity, and clinical status. The immunizations were well tolerated, and increasing doses of dHER2 had no impact on the frequency or severity of adverse events. Few late toxicities were reported, and after 5 years 45/54 patients (83.3 %) were still alive, while 28/45 (62 %) with known disease status were disease free. Regarding the immunogenicity of the compound, a positive association was found between the dHER2 dose, the immunization schedule, and the prevalence of dHER2-specific humoral responses. Among the patients receiving the most intense immunization schedule with the highest dHER2 dose, 6/8 maintained their dHER2-specific antibody response 5 years after immunization. The dHER2 immunotherapeutic had an acceptable safety profile in early HER2-positive BC patients. dHER2-specific antibody responses were induced, with the rate of responders increasing with the dHER2 dose and the number and frequency of immunizations.