Abstract 2899: Immunologic effects of a HER2 peptide (GP2) vaccine booster in previously vaccinated breast cancer patients

Background: We have conducted clinical trials of the HER2 peptide GP2 (MHC Class I restricted) vaccine in clinically disease-free breast cancer patients. Our Phase I/II trials showed the GP2+GM-CSF vaccine to be safe and effective in stimulating clonal expansion of GP2-specific cytotoxic CD8+ T-cells (GP2-CTLs) with anti-tumor activity. Here, we present data regarding the safety and immunologic response to boosters following completion of the primary vaccination series (PVS). Methods: Following completion of their PVS, patients enrolled on our phase II trial were administered booster inoculations every 6 months for 4 doses (500mcg GP2 peptide + 125mcg GM-CSF in the vaccine group (VG) or 125mcg GM-CSF alone in the control group (CG)). HLA A2- controls from the parallel study arm evaluating the HER2 peptide AE37 (MHC Class II restricted) vaccine were also eligible for evaluation as an extended CG (ECG). Patients were monitored for local and systemic toxicity, local reactions (LR) were measured, and GP2-CTLs were quantified using the HLA-A2:IgG dimer assay. Results: We have enrolled 294 patients (83 VG, 66 CG, and 145 ECG). Forty-six VG and 104 control (CG + ECG) have received booster doses. Boosters were well tolerated overall with toxicities comparable between VG and CG+ECG (Local: Gr 0: 2% vs 2%, Gr 1: 85% vs 93%, Gr 2: 13% vs 9%; Systemic: Gr 0: 52% vs 52%, Gr 1: 46% vs 45% , Gr 2: 0% vs 2%, Gr 3: 2% vs 1% ). Mean LR increased from booster 1 (B1) to booster 4 (B4) in the VG (B1: 63.8mm, B2: 66.0mm, B3: 85.2mm, B4: 72.6mm) and declined in the CG (B1: 47.8mm, B2: 43.8mm, B3: 40.2mm, B4: 37.8mm). Patients receiving B1 at 6 months after PVS in the VG group (n=46) were defined as early booster (EB, n=30), and those receiving B1 >6 months after PVS were defined as late booster (LB, n=16). GP2-CTLs prior to B1 were lower in LB patients (LB, 0.55±0.17 vs. EB, 1.00±0.16, p=0.07). Post-booster GP2-CTLs were compared between LB and EB at B1 (0.99±0.15 vs. 1.17±0.25, p=0.82), B2 (0.68±0.11 vs. 0.92±0.21, p=0.32), B3 (0.79±0.13 vs. 2.30±0.64, p=0.003), and B4 (1.08±0.43 vs. 3.37, p=na) respectively. EB post-booster GP2-CTLs levels were greater than LB at all time points although both groups sustained an increase in GP2-CTLs throughout the booster series. Conclusions: The GP2 peptide vaccine and boosters are safe with toxicities likely attributable to GM-CSF. The GP2 vaccine elicits a strong HER2-specific immune response that can be maintained with boosters. Based on t