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

Jean Charles Soria, Christophe Massard, Vladimir Lazar, Marie Laure Ozoux, Dominique Mery-Mignard, Antoine Deslandes, Anthony W. Tolcher

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    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 75 mg/m2 (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) 18 mg/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 12 mg/kg. The dose selected for further combinations is 6 mg/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 ≥4 months. Conclusion: AVE1642 is well tolerated as a single agent and combined with D. The selected dose of AVE1642 combined with D is 6 mg/kg. Promising activity was seen in sarcoma and breast cancer patients.

    Original languageEnglish
    Pages (from-to)1799-1807
    Number of pages9
    JournalEuropean Journal of Cancer
    Volume49
    Issue number8
    DOIs
    Publication statusPublished - 1 May 2013

    Keywords

    • Breast cancer
    • IGF-1
    • IGF-1R
    • Monoclonal antibody
    • Sarcoma

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