A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer

• Published in: Breast cancer research and treatment Vol. 156; no. 2; pp. 301 - 310
• Main Authors: Curigliano, Giuseppe, Romieu, Gilles, Campone, Mario, Dorval, Thierry, Duck, Lionel, Canon, Jean-Luc, Roemer-Becuwe, Celia, Roselli, Mario, Neciosup, Silvia, Burny, Wivine, Callegaro, Andrea, de Sousa Alves, Pedro Miguel, Louahed, Jamila, Brichard, Vincent, Lehmann, Frédéric F.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2016; Springer; Springer Nature B.V
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - therapy; Cancer metastasis; Cancer research; Cancer therapies; Clinical Trial; Clinical trials; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Immunotherapy; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Oncology; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Studies; Trastuzumab - administration & dosage; Trastuzumab - therapeutic use; Treatment Outcome; Vaccines; Cancer immunotherapeutic; HER2 antigen; Breast cancer; Vaccine
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-016-3750-y

The objectives of this phase I/II study (NCT00140738) were to evaluate the safety and clinical activity of a cancer immunotherapeutic agent (recombinant HER2 protein (dHER2) and the immunostimulant AS15) in patients with HER2-overexpressing metastatic breast cancer (MBC). Forty HER2-positive MBC patients received up to 18 doses (12q2w, 6q3w) of dHER2 immunotherapeutic, as first- or second-line therapy following response to trastuzumab-based treatment as maintenance. Toxicity was graded by the Common Terminology Criteria for Adverse Events (CTCAE) and clinical activity was evaluated by target lesion assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST). Immunogenicity was assessed. The dHER2 immunotherapeutic was well tolerated: grade 1/2 adverse events (AEs) were most common. No cardiac events were observed and one patient experienced an asymptomatic decrease of left ventricular ejection fraction below the normal range (47 %). Both humoral and cellular immunogenicity to the dHER2 antigen was observed. No patient discontinued the immunizations because of AEs but 35/40 withdrew prematurely, 34 because of disease progression (24/34 before or at the tumor assessment after dose 6). One patient achieved a complete response lasting 11 months and one patient had a partial response lasting 3.5 months. Ten patients experienced stable disease ≥26 weeks with 4/10 still in stable disease at the last tumor assessment after 47 weeks. Immunization of MBC patients with the dHER2 immunotherapeutic was associated with minimal toxicity and no cardiac events. Clinical activity was observed with two objective responses and prolonged stable disease for 10/40 patients.