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.
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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
May 2013
Université Paris XI, SITEP (Service des Innovations Thérapeutiques Précoces), Département de Médecine, Institut Gustave Roussy, Villejuif, France.
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.
Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors.
Ann Oncol
March 2013
Department of Oncology, Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford OX3 7LE, UK.
Background: Type 1 insulin-like growth factor receptor (IGF-1R) mediates resistance to chemotherapy and targeted agents. This study assessed the safety, pharmacokinetics (PK), and tolerability of humanized IGF-1R antibody AVE1642 with other cancer treatments.
Patients: Patients with advanced solid tumors received three weekly AVE1642 dosed at 6 mg/kg, chosen following previous study, with 75 (cohort A) or 100 mg/m(2) (B) docetaxel, 1250 mg/m(2) gemcitabine/100 mg erlotinib (C1), or 60 mg/m(2) doxorubicin (D1).
Targeting the insulin-like growth factor I receptor inhibits proliferation and VEGF production of non-small cell lung cancer cells and enhances paclitaxel-mediated anti-tumor effect.
Lung Cancer
August 2011
Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
The effects of AVE1642, a human monoclonal antibody against IGF-IR, were examined in NSCLC cell lines in order to characterize its anti-proliferative and anti-angiogenic activity as a single agent and in combination with chemotherapy. AVE1642 inhibited IGF-IR signaling and suppressed IGF-I-induced, serum-stimulated or autocrine-mediated proliferation of NSCLC cells in vitro. Furthermore, the combination of paclitaxel and AVE1642 resulted in a sequence-dependent increase in the inhibition of cell proliferation, compared to each agent alone, which was associated with a dose-dependent increase in phosphorylated IGF-IR and Akt.
View Article and Find Full Text PDFAnti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumour activity alone and in combination with temozolomide against neuroblastoma.
Eur J Cancer
December 2010
UPRES EA 3535, Pharmacology and New Treatments of Cancer, Université Paris-Sud XI, Institut Gustave Roussy, 94805 Villejuif, France.
Insulin-like growth factor 1 receptor (IGF-1R) is overexpressed in many tumours and contributes to tumourigenicity, cell proliferation, metastasis and resistance, thus representing a promising therapeutic target. The human IGF-1R antagonistic monoclonal antibody EM164 (murine AVE1642) has shown activity in adult cancers and is being evaluated in patients with advanced malignancies. We investigated the EM164 for its therapeutic potential against childhood neuroblastoma.
View Article and Find Full Text PDFSequencing of type I insulin-like growth factor receptor inhibition affects chemotherapy response in vitro and in vivo.
Clin Cancer Res
April 2009
Department of Pharmacology and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Purpose: The aim of this study was to determine the optimal sequence of combining anti-type I insulin-like growth factor receptor (IGF1R) antibodies with chemotherapeutic drugs in cancer cells in vitro and in vivo.
Experimental Design: MCF-7 and LCC6 cells were treated with subcytotoxic concentrations of doxorubicin with or without anti-IGF1R antibodies (scFv-Fc or EM164 and its humanized version AVE1642). Treatments were given simultaneously, doxorubicin followed by anti-IGF1R antibody, or anti-IGF1R antibody followed by doxorubicin, with measurement of in vitro proliferation, apoptosis, and anchorage-independent growth.
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