Results of the First Phase 1 Clinical Trial of the HER-2/neu Peptide (GP2) Vaccine in Disease-Free Breast Cancer Patients

BACKGROUND: HER-2/neu, overexpressed in breast cancer, is a source of immunogenic peptides that include GP2 and E75. Phase 2 testing of E75 as an adjuvant vaccine has suggested a clinical benefit. GP2, derived from the transmembrane portion of HER-2/neu, has differing binding characteristics and may be more immunogenic than E75. Results of the first phase 1 trial of GP2 peptide vaccine are presented. METHODS: Disease-free, lymph node-negative, human leukocyte antigen (HLA)-A2(+) breast cancer patients were enrolled. This dose escalation trial included 4 groups to determine safety and optimal GP2 peptide/granulocyte-macrophage colony-stimulating factor (GM-CSF) dose. Toxicities were monitored. Immunologic response was assessed ex vivo via the HLA-A2:immunoglobulin dimer assay to detect GP2-specific CD8(+) T cells (and E75-specific CD8+ T cells to assess epitope spreading) and in vivo via delayed type hypersensitivity (DTH) reaction (medians/ranges). RESULTS: Eighteen patients were enrolled. All toxicities were grade <= 2. Eight (88.9%) of 9 patients in the first 3 dose groups required GM-CSF dose reductions for local reactions >= 100 mm or grade >= 2 systemic toxicity. GM-CSF dose was reduced to 125 jig for the final dose group. All patients responded immunologically ex vivo (GP2-specific CD8(+) T cells from prevaccination to maximum, 0.4% [0.0%-2.0%] to 1.1% [0.4%-3.6%], P < .001) and in vivo (GP2 pre- to postvaccination DTH, 0 mm [0.0-19.5 mm] to 27.5 mm [0.0-114.5 mm, P < .001]. E75-specific CD8(+) T cells also increased in response to GP2 from prevaccination to maximum (0.8% [0.0%-2.41%] to 1.6% [0.86%-3.72%], P < .001). CONCLUSIONS: The GP2 peptide vaccine appears safe and well tolerated with minimal local/systemic toxicity. GP2 elicited HER-2/neu-specific immune responses, including epitope spreading, in high-risk, lymph node-negative breast cancer patients. These findings support further investigation of the GP2 vaccine for the prevention of breast cancer recurrence. Cancer 2010;116:292-301. (C) 2070 American Cancer Society.