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

Eur J Cancer. 2013 May;49(8):1799-807. doi: 10.1016/j.ejca.2013.01.003. Epub 2013 Feb 26.

Abstract

Purpose: 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).

Material and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Diarrhea / chemically induced
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Receptor, IGF Type 1 / immunology
  • Receptor, IGF Type 1 / metabolism
  • Sarcoma / drug therapy
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Treatment Outcome
  • Vomiting / chemically induced
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Taxoids
  • Docetaxel
  • Receptor, IGF Type 1
  • AVE1642