Interim Analysis of a Randomized Phase II Study of the Novel HER2/<i>Neu</i> Peptide (GP2) Vaccine To Prevent Breast Cancer Recurrence: United States Military Cancer Institute Clinical Trials Group Study I-05. (2009)

Abstract BACKGROUND: HER2/neu-derived peptides that stimulate CD8+ T-lymphocytes are being evaluated in vaccine trials. We present results of a prospective, randomized, single-blinded phase II clinical trial of a HLA-A2/A3-restricted, HER2/neu peptide (GP2, HER2/neu 654-662) + GM-CSF immunoadjuvant vaccine versus GM-CSF alone in disease-free, high risk breast cancer (BCa) patients to prevent disease recurrence.METHODS: Disease-free, high risk BCa patients who have completed standard adjuvant therapy were enrolled and randomized to receive six monthly inoculations of either 500 mcg of GP2 with 125 mcg of GM-CSF (Peptide group; PG) or 125 mcg of GM-CSF alone (adjuvant group; AG). Toxicity was assessed after each inoculation. Immunologic response was monitored by measured delayed type hypersensitivity reactions (DTH) and an HLA-A2:Immunoglobulin dimer assay to detect GP2-specific CD8+ T-lymphocytes. Patients were monitored clinically, radiographically, and pathologically for recurrence.RESULTS: Thus far, 50 (27 PG, 23 AG) of the planned 200 patients have completed the primary series. The PG and AG have similar demographic/prognostic characteristics (Table 1). Toxicity profiles in the PG and AG were nearly identical with no grade 4-5 local toxicities and no grade 3-5 systemic toxicities in either arm. Median DTH reaction to GP2 increased significantly from pre-vaccination level after completion of the primary series (post-vaccination) in the PG group (1.0±0.8 cm to 18.0 ±3.1 cm; p&lt;0.0001) and to a lesser extent in the AG group (0.0±1.0 cm to 0.5±3.3 cm; p&lt;0.01). The post-vaccination DTH was significantly larger in the PG compared to the AG (18.0 ±3.1 cm vs 0.5±3.3 cm, p=0.002). All (27/27) PG patients displayed significant immunity (SI) by DTH (reaction larger than 1 cm) post-vaccination compared 45.5% (10/22) of AG patients. Of the 10 AG patients with post-vaccination SI, 50% (5/10) had pre-vaccination SI compared to just 16.6% (2/12) without SI post-vaccination (p=0.38). The % GP2-specific CD8+ lymphocytes significantly increased from baseline at 6 months after completion of the primary series in the PG (0.65±0.15 to 1.82± 0.23, p=0.002) and did not change significantly in the AG (1.08 ± 0.16 to 1.41 ± 0.49, p=0.45). At a median follow up of 17.9 months, the recurrence rate in the PG is 7.4% (2/27) compared to 13% (3/23) in the AG (p=0.65).CONCLUSIONS: The HER2/neu peptide GP2 is safe with the mild toxicities primarily due to the GM-CSF immunoadjuvant. GP2 + GM-CSF elicits a strong in vivo response, while GM-CSF alone may expand in vivo immune response in patients with pre-existing GP2-specific immunity. Additionally, GP2+ GM-CSF expands HER2/neu-specific CD8+ T-lymphocytes ex vivo. Additional study will be required to determine if there is a clinical benefit to GP2 vaccination.Table 1: Demographics PeptideAdjuvantp=N=2723 Age (median)52510.88Node Positive51.9%69.6%0.32Grade 351.9%56.5%1Tumor &gt;= 2 cm66.7%52.2%0.45ER/PR negative40.7%43.5%0.92HER2 over-expressor59.3%47.8%0.60 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5110.