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

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.

• Authors: Jean Charles Soria, Christophe Massard, Vladimir Lazar, Marie-Laure Ozoux, Dominique Mery-Mignard, Antoine Deslandes, Anthony W Tolcher
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 49 Issue 8 Pg. 1799-807 (May 2013) ISSN: 1879-0852 [Electronic] England
• PMID: 23485230 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Area Under Curve
• Breast Neoplasms (drug therapy, metabolism, 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, metabolism, pathology)
• Receptor, IGF Type 1 (immunology, metabolism)
• Sarcoma (drug therapy, metabolism, pathology)
• Taxoids (administration & dosage, adverse effects)
• Treatment Outcome
• Vomiting (chemically induced)
• Young Adult