Symphogen A/S announced the initiation of a phase II clinical trial to investigate the safety and efficacy of Sym004 in patients who have failed anti-EGFR monoclonal antibody (mAb)-based therapy, with recurrent and/or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN). In June 2011 Symphogen completed the enrollment of patients in another study to evaluate the safety, efficacy and PK of Sym004 in patients with advanced metastatic colorectal cancer (mCRC) and wild-type KRAS.

The phase II clinical trial is an open label, single arm, multi-centre trial study in patients with SCCHN, who will receive weekly infusions of Sym004. The primary endpoint will be progression free survival at 24 weeks. Secondary endpoints include objective tumour response, time to progression, biomarkers, pharmacokinetic profile, and safety.

The trial was initiated at the Antwerp University Hospital, Belgium. Additional sites are expected to be opened in Belgium, Germany, France and the US.

Kirsten Drejer, M.Sc. and Ph.D., chief executive officer of Symphogen commented: “The preclinical data published in Cancer Research and Clinical Cancer Research, as well as the phase I data presented at ASCO 2011, hold great promise for Sym004, and we are very excited about advancing this compound into clinical evaluation for treatment of SCCHN as well as mCRC in patients who have failed anti-EGFR antibody based therapy.”

“Patients with advanced SCCHN and progressive disease after treatment with surgery, radiotherapy, chemotherapy and anti-EGFR mAb’s have few treatment alternatives today. Based on the pre-clinical results, it’s new mechanism of action and preliminary phase I data, I believe that Sym004 has the potential to induce tumour responses and provide this severely ill and poor prognosis population with a treatment option” stated coordinating investigator Professor Jean-Pascal Machiels, Cliniques Universitaires St-Luc, Centre du Cancer, Brussels, Belgium.

Sym004 is composed of two anti-EGFR mAbs targeting different non-overlapping epitopes. Sym004 not only blocks ligand binding, receptor activation/phosphorylation and downstream signaling but also shows a unique ability to induce rapid and efficient removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation. Sym004 also has the potential to treat tumours with acquired resistance to other EGFR-targeted agents. The preliminary data from the clinical phase I study indicate that only the expected adverse event profile of EGFR target mAb therapeutics was observed, i.e. diarrhoea, rash, mucosal inflammation, nausea, infusion related reaction and hypomagnesemia. Exposure data from the patients, after weekly repeated infusions, do not indicate an anti-drug antibody response.

Symphogen is developing superior antibody therapeutics (monoclonal, monoclonal mixtures and polyclonal) to help people with serious diseases and significant unmet medical needs.