A global leader in optimizing the sugar chains (glycosylation) of biopharmaceuticals, announced full details of first-in-man Phase I trial data for CetuGEX™, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with optimized and fully human glycosylation for a greatly enhanced anti-tumor activity and reduced side-effects. The data was presented on Monday at ASCO 2013 in the Developmental Therapeutics and Immunotherapy Session. In the Phase I trial, 41 patients were treated with various doses of CetuGEX™ to evaluate the safety and tolerability profile of this novel compound and to define the recommended Phase II dosing regimen. Secondary endpoints included the preliminary evaluation of anti-tumor activity of CetuGEX™. In conclusion, CetuGEX™ was well tolerated with a favourable side-effect profile clearly lower than those observed with other EGFR-targeting molecules and showed clear signs of therapeutic activity as a single agent.
Activity was seen over all dose levels, with a clinical benefit rate of 76% (19/25) in the per protocol population in this single agent study. All patients were progressive upon inclusion into the study and heavily pre-treated with 78% having received three or more prior chemotherapies. Four major clinical and RECIST responses were observed besides long lasting disease stabilization, including two complete and two partial responders in non-small cell lung cancer (NSCLC), metastatic colorectal cancer, esophageal and gastric cancer. All responders show continuing sustained responses and hence are still under treatment, with the longest duration of over 18 months (Complete Responder stage IV NSCLC). Additional 15 patients achieved sustained stable disease lasting from eight weeks to over 14 months. CetuGEX™ showed a favourable side-effect profile with few occurrence and low grades of EGFR-typical toxicities, including acneiform skin rashes in 25% of patients and no skin reactions of grade 3 or higher as well as ≤10% low grades of digestion track toxicities. Infusion reactions were restricted to the first infusions only and occurred in 57% with the final dosing schedule. Pharmacokinetic data allow weekly or two-weekly administration schedules. Clinical trial information: NCT01222637.
Prof. Dr. Walter Fiedler from University Hospital Hamburg-Eppendorf, who presented the results of the study, concluded his presentation saying, that CetuGEX™ showed high tolerability and clear signs of anti-cancer activity as a single agent and should be further developed in Phase II. Steven R. Alberts, M.D., from Mayo Clinic in Rochester, the discussant of the study, highlighted the activity in heavily pretreated cancer patients and concluded that CetuGEX™ results suggest a more tolerable EGFR antibody which he recommended to develop further in clinic studies.
The full abstract can be found at: http://abstract.asco.org/index.html
Monoclonal antibody CetuGEX™, glycooptimized GT-MAB 5.2-GEX™, is a BioSuperior EGFR antibody for treatment of NSCLC, metastatic colorectal
cancer (CRC), head and neck cancers as well as esophageal and gastric cancers. CetuGEX™ is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with optimized and fully human glycosylation. It expresses several anti-tumor modes of action, a very strong antibody dependent cellular toxicity (ADCC), efficient proliferation inhibition via receptor blockage and apoptosis induction. Based on the optimization of a series of sugar determinants CetuGEX™ is 10 to 250-fold more active in anti-tumor ADCC compared to Cetuximab making it highly potent for patients of all ADCC receptor allotypes and KRAS mutant patients. The molecule has an optimized bioavailability, lacks foreign immunogenic carbohydrates and has shown a largely improved side-effect profile compared to other EGFR antibodies such as low grade and low incidence of skin rash. These improvements aim for an expansion of the number of suitable patients as well as indications. Phase IIb clinical development is due to start in summer 2013.
Glycotope, founded in 2001 in Berlin, focuses on the development of innovative antibodies for the treatment of various cancer types. These GlycoBodies target glycostructures on cell surfaces. In addition, Glycotope develops so-called BioSuperiors, antibody and non-antibody recombinant biopharmaceuticals with optimized and fully human sugar structures for clinical superiority. Key to the glycooptimization technology is a toolbox of glycoengineered proprietary human cell lines that allow the glycooptimization of proteins in respect to a whole series of different determining sugars and is based on fully human glycosylation. GlycoExpress allows the selection of the most appropriate and best suitable human glycoform of a product and a high yield production superior in reproducibility, quality and yield. Glycooptimization via GlycoExpress provides improved efficacy, bioavailability, immunogenicity and broadens the potential patient populations and indications, as well as providing a much improved cost-effectiveness. Glycotope has currently four products in clinical development from late stage Phase I to late stage Phase II. The Company’s additional pipeline includes preclinical non-antibody and antibody biopharmaceuticals for various indications.
Together with Glycotope Biotechnology in Heidelberg, Glycotope has evolved into a leading fully integrated glycobiology company, covering all phases discovery, preclinical and clinical drug development and GMP production. With more than 150 employees and a strong and broad IP-platform, Glycotope has grown to one of the largest biotechnology companies in Germany.