Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients

Ann Oncol. 2014 Sep;25(9):1735-1742. doi: 10.1093/annonc/mdu211. Epub 2014 Jun 6.


Background: E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses.

Patients and methods: The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.

Results: Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%).

Conclusion: The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated.

Clinical trials: NCT00841399, NCT00584789.

Keywords: breast cancer; immunotherapy; nelipepimut-S; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Aged
  • Breast / pathology
  • Breast Neoplasms / immunology*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Disease-Free Survival
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • HLA-A2 Antigen / immunology
  • HLA-A3 Antigen / immunology
  • Humans
  • Immunization, Secondary
  • Immunotherapy / methods*
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / metabolism
  • Vaccination


  • Adjuvants, Immunologic
  • Cancer Vaccines
  • HLA-A2 Antigen
  • HLA-A3 Antigen
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data