Breast Cancer Research and Treatment

, Volume 156, Issue 2, pp 301–310 | Cite as

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

  • Giuseppe Curigliano
  • Gilles Romieu
  • Mario Campone
  • Thierry Dorval
  • Lionel Duck
  • Jean-Luc Canon
  • Celia Roemer-Becuwe
  • Mario Roselli
  • Silvia Neciosup
  • Wivine Burny
  • Andrea Callegaro
  • Pedro Miguel de Sousa Alves
  • Jamila Louahed
  • Vincent Brichard
  • Frédéric F. Lehmann
Clinical trial


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.


Breast cancer Cancer immunotherapeutic HER2 antigen Vaccine 





Adverse events


Breast cancer


Clinical benefit rate


Cell-mediated immunogenicity


Complete response


Common Terminology Criteria for Adverse Events


Extracellular domain


Eastern Cooperative Oncology Group


Enzyme-linked immunosorbent assays


Geometric mean concentrations


Human epidermal growth factor receptor 2


Intracellular domain


Left ventricular ejection fraction


Metastatic breast cancer


Peripheral blood mononuclear cells


Partial response


Response evaluation criteria in solid tumors


Serious adverse event


Stable disease



The authors thank the patients who participated in this study and their families. They also acknowledge the investigators and their clinical teams for their contribution to the study and their support and care of patients, in particular Thomas Bachelot, Henri Roche and Jaak Janssens. The authors thank the global and regional clinical operations and safety teams of GSK for their contribution to the study, the scientific writer for clinical protocol and clinical report writing and the team of statisticians at GSK for the statistical analysis. The authors thank Françoise Cormont, Valentine Wascotte and Anne-Laure Puaux for critical reading of the paper and helpful suggestions. The authors thank Niels Neymark (medical writer on behalf of GSK) for assistance in the manuscript writing, and Sophie Timmery (XPE Pharma & Science) for coordination and editorial assistance.

Author contributions

Study conception and design Vincent Brichard, Frédéric F. Lehmann, Jamila Louahed, Andrea Callegaro. Collection and assembly of data Giuseppe Curigliano, Gilles Romieu, Lionel Duck, Célia Roemer-Becuwe, Mario Roselli, Silvia Neciosup, Jean-Luc Canon. Data analysis and interpretation Vincent Brichard, Frédéric F. Lehmann, Jamila Louahed, Wivine Burny, Giuseppe Curigliano, Pedro Miguel de Sousa Alves, Andrea Callegaro, Lionel Duck, Mario Campone. Provision of study materials or patients Giuseppe Curigliano, Gilles Romieu, Silvia Neciosup, Mario Campone.


Employment Pedro Miguel De Sousa Alves (GSK group of companies); Frédéric F. Lehmann (GSK group of companies); Jamila Louahed (GSK group of companies); Vincent G. Brichard (GSK group of companies); Wivine Burny (GSK group of companies); Andrea Callegaro (GSK group of companies). Stock ownership Frédéric F. Lehmann (GSK group of companies); Jamila Louahed (GSK group of companies); Vincent G. Brichard (GSK group of companies); Pedro Miguel De Sousa Alves (GSK group of companies). Honoraria Mario Campone (Novartis, Servier, Menar). Consultant or advisory role Mario Campone (Novartis, Servier, Menar), Jean-Luc Canon (GSK). Speakers’ bureau Gilles Romieu (GSK, Roche), Mario Campone (Novartis). Research funding Mario Campone’s institution (Novartis). Expert testimony: Gilles Romieu (Roche). Travel, accommodations, expenses Gilles Romieu (Amgen), Mario Campone (Novartis).


This work was supported by GlaxoSmithKline Biologicals SA that was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also funded all costs associated with the development and the publishing of the present manuscript. All authors had full access to the data and the corresponding author was responsible for submission of the publication.

Compliance with ethical standards

Conflict of interest

Giuseppe Curigliano, Lionel Duck, Célia Roemer-Becuwe, Mario Roselli, Silvia Neciosup, Thierry Dorval declare that they have no conflict of interest.

Supplementary material

10549_2016_3750_MOESM1_ESM.pdf (159 kb)
Supplementary material 1 (PDF 159 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Giuseppe Curigliano
    • 1
  • Gilles Romieu
    • 2
  • Mario Campone
    • 3
  • Thierry Dorval
    • 4
  • Lionel Duck
    • 5
  • Jean-Luc Canon
    • 6
  • Celia Roemer-Becuwe
    • 7
  • Mario Roselli
    • 8
  • Silvia Neciosup
    • 9
  • Wivine Burny
    • 10
  • Andrea Callegaro
    • 10
  • Pedro Miguel de Sousa Alves
    • 10
  • Jamila Louahed
    • 10
  • Vincent Brichard
    • 10
  • Frédéric F. Lehmann
    • 10
  1. 1.Early Drug Development for Innovative Therapies DivisionIstituto Europeo di Oncologica di MilanoMilanItaly
  2. 2.Institut régional du Cancer de MontpellierMontpellierFrance
  3. 3.Institut de Cancérologie de l’OuestNantesFrance
  4. 4.Department of Medical OncologyInstitut CurieParisFrance
  5. 5.Department of Medical OncologyClinique Saint-PierreOttigniesBelgium
  6. 6.Oncology-Hematology DepartmentGrand Hopital de CharleroiCharleroiBelgium
  7. 7.Centre d’Oncologie de GentillyNancyFrance
  8. 8.Medical Oncology Unit‘Tor Vergata’ University HospitalRomeItaly
  9. 9.Instituto Nacional de Enfermedades NeoplásicasLimaPeru
  10. 10.GSK VaccinesRixensartBelgium

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