title: A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity.
  
  
  RESULTS
  Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 1-39 %). The median duration of progression-free survival was 82 days (95 % CI 41-140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 7-27 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected.
  
  
  CONCLUSIONS
  The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.
authors.affiliation: Institut Roi Albert II, Service d'oncologie médicale, Cliniques universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, 10 Avenue Hippocrate, 1200, Brussels, Belgium, jean-pascal.machiels@uclouvain.be.
authors.forename: J-P
authors.initials: JP
authors.lastname: Machiels
authors.forename: P
authors.initials: P
authors.lastname: Specenier
authors.forename: J
authors.initials: J
authors.lastname: Krauß
authors.forename: A
authors.initials: A
authors.lastname: Dietz
authors.forename: M-C
authors.initials: MC
authors.lastname: Kaminsky
authors.forename: Y
authors.initials: Y
authors.lastname: Lalami
authors.forename: M
authors.initials: M
authors.lastname: Henke
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
authors.forename: R
authors.initials: R
authors.lastname: Knecht
authors.forename: N J
authors.initials: NJ
authors.lastname: Skartved
authors.forename: I D
authors.initials: ID
authors.lastname: Horak
authors.forename: P
authors.initials: P
authors.lastname: Pamperin
authors.forename: S
authors.initials: S
authors.lastname: Braun
authors.forename: T C
authors.initials: TC
authors.lastname: Gauler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology; D045744:Cell Line, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; C569270:futuximab; C512478:EGFR protein, human; D066246:ErbB Receptors