ImClone Systems Incorporated, a global leader in the development and commercialisation of novel antibodies to treat cancer, said a phase II clinical trial of its anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody IMC-A12 in patients with head and neck cancer has commenced patient enrolment.

This randomised, dual-arm phase II study will evaluate IMC-A12 as a single agent and in combination with Erbitux (cetuximab) in patients with metastatic head and neck cancer who have failed prior platinum-based treatment. Up to 90 patients are expected to be enrolled. Based on supportive preclinical data indicating favourable anticancer interactions when IMC-A12 and Erbitux are combined, this phase II study is designed to evaluate the efficacy, safety and pharmacology effects of IMC-A12 as a single agent and in combination with Erbitux. In addition to traditional Phase II endpoints, the effects of IMC-A12 and Erbitux on many potential cellular targets of IMC-A12 and Erbitux will be assessed by several academic institutions that hold National Cancer Institute (NCI) Special Programmes of Research Excellence (SPORE) grants in head and neck cancer, which are among the wide variety of treatment centres participating in this trial.

"This disease-directed study of IMC-A12 in combination with Erbitux builds on the solid foundation of positive Erbitux data in the head and neck cancer treatment setting, as well as a strong preclinical rationale indicating that targeting both the insulin-like growth factor receptor and epidermal growth factor receptor with IMC-A12 and Erbitux, respectively, may result in favourable anticancer interactions," said Eric K. Rowinsky, M.D., chief medical officer and executive vice president, ImClone. "This study will evaluate whether the efficacy results observed with Erbitux in head and neck cancer patients with locally-advanced, recurrent and metastatic disease may be enhanced by combining IMC-A12."


IMC-A12 is a fully human IgG1 monoclonal antibody. It is designed to specifically target the human IGF-1R, thereby inhibiting certain ligands known as IGFs I and II from binding to and activating the receptor. This action blocks a signalling pathway that enhances tumour cell proliferation and survival. In 2007, ImClone completed enrolment into two phase I studies of IMC-A12, which demonstrated favourable safety and pharmacokinetic profiles, as well as preliminary evidence of anti tumour activity as a single agent when administered either weekly or every two weeks. In addition to this phase II study of IMC-A12 in patients with head and neck cancer, disease-directed studies of IMC-A12 in patients with advanced prostate and colorectal cancers, as well as paediatric malignancies have begun to enrol patients.

"Throughout the first quarter of 2008 we have continued our progress in rapidly advancing our pipeline of novel antibodies, which is a key component of our long-term strategy to grow organically and further solidify our position as a leading fully-integrated global biotechnology company," said John H. Johnson, chief executive officer, ImClone. "This study in particular also exemplifies our efforts to maximise the full potential of the Erbitux franchise in developing new treatment options for patients with cancer."

Erbitux is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumour cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown that binding of Erbitux to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production. In vitro, Erbitux can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. No anti-tumour effects of Erbitux were observed in human tumour xenografts lacking EGFR expression. EGFR is part of a signalling pathway that is linked to the growth and development of many human cancers, including those of the head and neck, colon and rectum.

Erbitux, as a single agent, is indicated for the treatment of EGFR-expressing mCRC after failure of both irinotecan- and oxaliplatin-based regimens. Erbitux, as a single agent, is also indicated for the treatment of EGFR-expressing mCRC in patients who are intolerant to irinotecan-based regimens.