A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN)

Cancer Immunol Immunother. 2015 Mar;64(3):367-79. doi: 10.1007/s00262-014-1640-x. Epub 2014 Dec 24.

Abstract

Background: We conducted a phase I dose escalation study to evaluate the safety and immunologic response to peptide immunomodulatory vaccines GL-0810 (HPV16) and GL-0817 (MAGE-A3) in HPV16 and MAGE-A3-positive RM-SCCHN patients, respectively.

Methods: Three dose levels (500, 1,000, and 1,500 µg) of GL-0810 or GL-0817 with adjuvants Montanide (1.2 ml) and GM-CSF (100 µg/m2) were administered subcutaneously q2 weeks for a total of four vaccinations in HPV16 and MAGE-A3-positive RM-SCCHN patients, respectively.

Results: Nine and seven patients were enrolled in the HPV16 and MAGE-A3 cohorts, respectively. No dose-limiting toxicities were observed, and toxicity was predominantly local and grade 1 (erythema, pain, and itching at the injection site). In those patients who received all four vaccinations, 80 % (4/5) of the HPV16 cohort and 67 % (4/6) of the MAGE-A3 cohort developed antigen-specific T cell and antibody responses to the vaccine. Significant concordance between T cell and antibody responses was observed for both groups. No clear dose-response correlation was seen. All patients progressed by RECIST at first repeat imaging, except for one patient in the MAGE-A3 500 µg cohort who had stable disease for 10.5 months. The median PFS and OS for the MAGE-A3 cohorts were 79 and 183 days, respectively, and for the HPV16 cohort 80 and 196 days, respectively.

Conclusions: GL-0810 and GL-0817 were well tolerated in patients with RM-SCCHN with T cell and antibody responses observed in the majority of patients who received all four vaccinations.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / therapy*
  • Cohort Studies
  • Disease Progression
  • Dose-Response Relationship, Immunologic
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / therapy*
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / immunology
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Squamous Cell Carcinoma of Head and Neck
  • Vaccines, Subunit / administration & dosage*
  • Vaccines, Subunit / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Immunologic Factors
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Vaccines, Subunit
  • Granulocyte-Macrophage Colony-Stimulating Factor