Abstract P5-16-02: Final Results of the Phase I/II Trials of the E75 Adjuvant Breast Cancer Vaccine
Authors: Vreeland TJ , Clifton GT , Hale DF , Sears AK , Patil R , Holmes JP , Ponniah S , Mittendorf EA , Peoples GE 
Published: August 2014

Abstract
Background: We have completed phase I/II clinical trials vaccinating breast cancer patients (pts) with E75, a HLA-A2/A3-restricted HER2/neu (HER2) peptide vaccine. The vaccine was administered in the adjuvant setting to prevent recurrences in high risk patients rendered disease-free with standard of care therapy. We have previously reported preliminary results indicating that the vaccine (including booster inoculations) is safe and effective in stimulating an anti-tumor immune response. Here, we report the final 5 year results from these trials.
Methods: The phase I/II trials were performed as dose-escalation/schedule-optimization trials enrolling node positive and high-risk, node negative breast cancer patients with tumors expressing any level of HER2. HLA-A2/A3+ pts were enrolled into the vaccine group (VG) while HLA-A2/A3- pts were followed prospectively as the untreated control group (CG). The VG pts were given 4–6 monthly intradermal inoculations of E75 with GM-CSF during the primary vaccine series (PVS). In addition, a voluntary booster program was initiated during the trial, with booster inoculations being offered every 6 months after completion of the PVS. Patients were monitored for local and systemic toxicity (graded by NCI Common Terminology Criteria for Adverse Events). In vivo immune response was assessed in the VG by delayed type hypersensitivity (DTH) reactions to both E75 and saline, pre- and post-PVS. VG and CG pts were followed for 60 months (mo) and recurrences were documented. Demographic differences were compared with the Fisher's exact test and disease-free survival was determined using the Kaplan-Meier method and compared by log-rank test.
Results: 195 pts were enrolled, 6 withdrew (2 from VG, 4 from CG), 1 was lost to follow-up prior to vaccination, and 1 was found to be ineligible, leaving 187 evaluable pts; 108 in the VG and 79 in the CG. 53 pts volunteered for the booster program and received at least one booster inoculation. The VG and CG were well-matched with the only statistically significant difference being ER−/PR- status (31.1% in VG vs 17.7% in CG, p = 0.04). Vaccination was well tolerated (maximum local toxicity: 73.1% Grade 1, 26.9% Grade 2, 0% Grade 3; maximum systemic toxicity: 72.2% Grade 1, 15.7% Grade 2, and 2.8% Grade 3). In the VG, pre- to post-PVS E75 DTH significantly increased (mean 3.8 ±1.0 vs 14.8±1.4, p &lt; 0.001) and post-PVS E75 DTH was significantly greater than post-PVS saline DTH (1.84±0.5 vs 14.8±1.4, p &lt; 0.001). At the end of the trial, analysis of the Kaplan Meier curves at 60 mo shows increased disease-free survival in the VG compared to the CG with a trend toward significance (89.7% vs 80.6%, p = 0.076).
Conclusions: The E75 breast cancer vaccine is safe and well–tolerated. It elicits strong immune responses in vaccinated patients. At the end of the 5 year follow-up period, the E75 vaccine shows a strong trend toward preventing breast cancer recurrence in vaccinated patients. To investigate this vaccine (now known as NeuVax) further, the PRESENT trial, a prospective, randomized, double-blind, placebo-controlled, multi-center phase III registration trial has been initiated and is actively enrolling.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-02.