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)

Dan P. Zandberg, Sandra Rollins, Olga Goloubeva, Robert E. Morales, Ming Tan, Rodney Taylor, Jeffrey S. Wolf, Lisa M. Schumaker, Kevin J. Cullen, Ann Zimrin, Robert Ord, Joshua E. Lubek, Mohan Suntharalingam, John C. Papadimitriou, Dean Mann, Scott E. Strome, Martin J. Edelman

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)367-379
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume64
Issue number3
DOIs
StatePublished - Feb 26 2015
Externally publishedYes

Keywords

  • Immune response
  • Peptide
  • Squamous cell carcinoma of the head and neck
  • Vaccine

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