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A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2-overexpressing tumors
A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2-overexpressing tumors
- Source :
- Breast cancer research and treatment, 156(2), 319-330. Springer New York
- Publication Year :
- 2016
-
Abstract
- 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 A mu g) 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
- Subjects :
- 0301 basic medicine
Oncology
Adult
Cancer Research
medicine.medical_specialty
medicine.drug_class
Receptor, ErbB-2
medicine.medical_treatment
Breast Neoplasms
Immunostimulant
Drug Administration Schedule
03 medical and health sciences
0302 clinical medicine
Breast cancer
Internal medicine
medicine
Adjuvant therapy
Humans
Immunologic Factors
Drug Dosage Calculations
Adverse effect
Survival analysis
Aged
Dose-Response Relationship, Drug
business.industry
Immunogenicity
Immunotherapy
Middle Aged
medicine.disease
Survival Analysis
Recombinant Proteins
Up-Regulation
Gene Expression Regulation, Neoplastic
030104 developmental biology
Treatment Outcome
Immunization
030220 oncology & carcinogenesis
Immunology
Female
business
Subjects
Details
- ISSN :
- 15737217 and 01676806
- Volume :
- 156
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Breast cancer research and treatment
- Accession number :
- edsair.doi.dedup.....60dbba5ebf38dec8c4d21adc444766ed