Date: 2011-08-23
Type of information: Initiation of preclinical development
phase: 2
Announcement: initiation
Company: Symphogen (Denmark)
Product: Sym004
Action
mechanism: 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 tumors with acquired resistance to other EGFR-targeted agents.
Disease: metastatic squamous cell carcinoma of the head and neck
Therapeutic area: Cancer Oncology
Country: Belgium, Germany, France, USA
Trial
details: The Phase 2 clinical trial is an open label, single arm, multi-center trial study in patients with squamous cell carcinoma of the head and neck, who will receive weekly infusions of Sym004. The primary endpoint will be progression free survival at 24 weeks. Secondary endpoints include objective tumor 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.
Latest
news: * On June 2, 2013, Symphogen, a private biopharmaceutical company developing recombinant antibody mixtures, has announced at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO) the results of two proof-of-concept studies of SYM004, an anti-EGFR monoclonal antibody (mAb) mixture. Symphogen entered the antibody mixture into the clinic in 2010, and subsequently partnered with Merck KGaA, in September 2012.
Squamous Cell Carcinoma of the Head and Neck (SCCHN) Phase 2 Open Label Study Results:
Weekly doses of 12 mg/kg Sym004 showed clinical response of stable disease in half of the heavily pretreated SCCHN patients resistant/refractory to previous anti-EGFR mAb treatment.
• Tumor shrinkage was observed in 8/26 patients by central and blinded review of CT scans. SD was observed in 13/26 patients.
• Median PFS was 2.7 months (95% CI 1.4-4.7 months).
• The observed safety profile was similar to other anti-EGFR mAbs except for skin related toxicity
• EGFR down-modulation was observed in paired skin and tumor biopsies, supporting the proposed mechanism-of-action.
As of 21-May-2013, 105 patients have been treated with Sym004 in clinical trials. The most frequently reported adverse events from the preliminary clinical data include, skin rash, dermatitis acneiform, erythema, nausea, fatigue hypocalcemia and hypomagnesemia. Exposure data from the patients, after weekly repeated infusions, do not indicate an anti-drug antibody response.
