Open Access Research

Phase I clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibtion

Erika Hamilton1, Kimberly Blackwell1, Amy C Hobeika2, Timothy M Clay3, Gloria Broadwater4, Xiu-Rong Ren5, Wei Chen5, Henry Castro3, Frederic Lehmann3, Neil Spector1, Junping Wei6, Takuya Osada6 and H Kim Lyerly2*

Author Affiliations

1 Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA

2 Department of Surgery, Division of General Surgery, Duke University Medical Center, Durham, NC, USA

3 GlaxoSmithKline Biologicals, Rixensart, Belgium

4 Cancer Statistical Center, Duke Cancer Institute, Durham, NC, USA

5 Department of Medicine, Division of Gastroenterology, Duke University Medical Center, Durham, NC, USA

6 Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, Durham, NC, USA

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Journal of Translational Medicine 2012, 10:28  doi:10.1186/1479-5876-10-28

Published: 10 February 2012



Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when combined with lapatinib in murine models. We wished to test the clinical safety, immunogenicity, and activity of a HER2-based cancer vaccine, when combined with lapatinib.


We immunized women (n = 12) with metastatic, trastuzumab-refractory, HER2-overexpressing breast cancer with dHER2, a recombinant protein consisting of extracellular domain (ECD) and a portion of the intracellular domain (ICD) of HER2 combined with the adjuvant AS15, containing MPL, QS21, CpG and liposome. Lapatinib (1250 mg/day) was administered concurrently. Peripheral blood antibody and T cell responses were measured.


This regimen was well tolerated, with no cardiotoxicity. Anti-HER2-specific antibody was induced in all patients whereas HER2-specific T cells were detected in one patient. Preliminary analyses of patient serum demonstrated downstream signaling inhibition in HER2 expressing tumor cells. The median time to progression was 55 days, with the majority of patients progressing prior to induction of peak anti-HER2 immune responses; however, 300-day overall survival was 92% (95% CI: 77-100%).


dHER2 combined with lapatinib was safe and immunogenic with promising long term survival in those with HER2-overexpressing breast cancers refractory to trastuzumab. Further studies to define the anticancer activity of the antibodies induced by HER2 vaccines along with lapatinib are underway.

Trial registry NCT00952692

HER2; Antitumor immunity; Immunization; Breast cancer