Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors

Clin Cancer Res. 2019 Jun 15;25(12):3495-3507. doi: 10.1158/1078-0432.CCR-18-3997. Epub 2019 Feb 25.


Purpose: This first-in-human phase I study (NCT01417546) evaluated the safety profile, optimal immunologic/biological dose (OID/OBD), and immunogenicity of the combination of two peptide B-cell epitope vaccines engineered to represent the trastuzumab- and pertuzumab-binding sites. Although trastuzumab and pertuzumab have been approved for clinical use, patients often develop resistance to these therapies. We have advanced a new paradigm in immunotherapy that focuses on humoral responses based on conformational B-cell epitope vaccines.

Patients and methods: The vaccine is comprised of two chimeric HER-2 B-cell peptide vaccines incorporating a "promiscuous T-cell epitope." Patients were immunized with the vaccine constructs emulsified with nor-muramyl-dipeptide adjuvant in a water-in-oil Montanide ISA 720VG vehicle. Eligible patients with metastatic and/or recurrent solid tumors received three inoculations every 3 weeks.

Results: Forty-nine patients with a median of 4 prior lines of chemotherapy received at least 1 vaccination. Twenty-eight patients completed the 3 vaccination regimens. Six patients received 1 six-month boost after the regimen, and one patient received 7 six-month boosts. No serious adverse reactions or dose-limiting toxicities were observed. The vaccine was well tolerated with dose level 2 as the recommended phase II dose. The most common related toxicity in all patients was injection-site reactions (24%). Two patients had a partial response, 14 had stable disease, and 19 had progressive disease.

Conclusions: The study vaccine is safe, exhibits antitumor activity, and shows preliminary indication that peptide vaccination may avoid therapeutic resistance and offer a promising alternative to monoclonal antibody therapies.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / chemistry
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Proliferation / drug effects
  • Cohort Studies
  • Epitopes, B-Lymphocyte / immunology*
  • Female
  • Humans
  • Immunization / methods
  • Male
  • Mannitol / analogs & derivatives*
  • Mannitol / chemistry
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Oleic Acids / chemistry*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / immunology*
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Vaccines, Subunit / administration & dosage*
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / immunology


  • Adjuvants, Immunologic
  • Epitopes, B-Lymphocyte
  • Oleic Acids
  • Vaccines, Subunit
  • mannide monooleate
  • Mannitol
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data