Dalotuzumab, a recombinant humanized mAb targeted against IGFR1 for the treatment of cancer

Curr Opin Mol Ther. 2010 Jun;12(3):361-71.

Abstract

Dalotuzumab (MK-0646; h7C10), being developed by Merck & Co Inc under license from Pierre Fabre SA, is a recombinant humanized IgG1 mAb against the IGFR1 for the potential intravenous treatment of cancer. Preclinical studies have demonstrated that dalotuzumab acts by inhibiting IGF-1- and IGF-2-mediated tumor cell proliferation, IGFR1 autophosphorylation and Akt phosphorylation. In multiple cancer cell lines and in mouse xenograft models, dalotuzumab displayed significant antitumor activity, in particular against NSCLC and breast cancer. In addition, coadministration of dalotuzumab with other anticancer agents, such as taxanes, enhanced the in vitro and in vivo antitumor activity of dalotuzumab. Preliminary data from phase I clinical trials suggest that dalotuzumab is safe, well tolerated and significantly inhibits tumor proliferation. At the time of publication, several clinical trials evaluating dalotuzumab, alone and in combination with other anticancer agents, were ongoing in patients with various types of solid tumor and in patients with multiple myeloma. Although preliminary results appear promising, only future clinical and translational data will clarify the best clinical setting and treatment combinations for the optimal use of dalotuzumab in clinical practice.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Combined Modality Therapy
  • Female
  • Humans
  • Insulin-Like Growth Factor I / therapeutic use
  • Insulin-Like Growth Factor II / therapeutic use
  • Mice
  • Mice, Nude
  • Multiple Myeloma / drug therapy
  • Neoplasms / drug therapy*
  • Nervous System Neoplasms / drug therapy

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • dalotuzumab