title: 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).
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.
authors.affiliation: University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene St. Rm N9E29, Baltimore, MD, 21201, USA, dzandberg@umm.edu.
authors.forename: Dan P
authors.initials: DP
authors.lastname: Zandberg
authors.forename: Sandra
authors.initials: S
authors.lastname: Rollins
authors.forename: Olga
authors.initials: O
authors.lastname: Goloubeva
authors.forename: Robert E
authors.initials: RE
authors.lastname: Morales
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Rodney
authors.initials: R
authors.lastname: Taylor
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wolf
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schumaker
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cullen
authors.forename: Ann
authors.initials: A
authors.lastname: Zimrin
authors.forename: Robert
authors.initials: R
authors.lastname: Ord
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Lubek
authors.forename: Mohan
authors.initials: M
authors.lastname: Suntharalingam
authors.forename: John C
authors.initials: JC
authors.lastname: Papadimitriou
authors.forename: Dean
authors.initials: D
authors.lastname: Mann
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D015331:Cohort Studies; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007155:Immunologic Factors; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor