title: A dose finding, safety and pharmacokinetic study of AVE1642, an anti-insulin-like growth factor-1 receptor (IGF-1R/CD221) monoclonal antibody, administered as a single agent and in combination with docetaxel in patients with advanced solid tumours.
abstract: OBJECTIVE
  AVE1642, a humanised mAb, binds the human IGF-1R specifically and with high affinity. This study aimed to select the dose of AVE1642 alone and then combined with docetaxel 75mg/m(2) (D).
  
  
  METHODS
  AVE1642 was administered alone at cycle (cy) 1 and then combined with D from cy2, q3w.
  
  
  RESULTS
  A total of 27 patients received a median number of 5 cy (range, 1-10). The most common tumour types were sarcoma (18.5%), osseous tumours (11.1%) and colon cancer (11.1%). Two DLTs were reported in cy1 at dose level (DL) 18mg/kg and dose escalation was stopped. No major safety issue was observed. No anti-drug antibodies were detected. The Maximal Tolerated Dose of AVE1642 was 12mg/kg. The dose selected for further combinations is 6mg/kg, based on PK/PD data. Three objective responses, (two in sarcoma and one breast cancer) were observed but only one was confirmed. Eleven patients appeared to benefit from treatment with prolonged disease stabilisation ⩾4months.
  
  
  CONCLUSIONS
  AVE1642 is well tolerated as a single agent and combined with D. The selected dose of AVE1642 combined with D is 6mg/kg. Promising activity was seen in sarcoma and breast cancer patients.
authors.affiliation: Université Paris XI, SITEP (Service des Innovations Thérapeutiques Précoces), Département de Médecine, Institut Gustave Roussy, Villejuif, France. soria@igr.fr
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ozoux
authors.forename: Dominique
authors.initials: D
authors.lastname: Mery-Mignard
authors.forename: Antoine
authors.initials: A
authors.lastname: Deslandes
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Tolcher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000276:immunology / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D017526:Receptor, IGF Type 1; C545477:AVE1642