Glyco-optimized second-generation cetuximab (Erbitux®)
Tomuzotuximab (previously known as CetuGEX®) is a novel best-in-class immune-enhanced monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) with optimized and fully human glycosylation. Tomuzotuximab works via several anti-tumor mechanisms of action: a strong antibody dependent cellular toxicity (ADCC), proliferation inhibition via receptor blockage and induction of apoptosis.
A study in Head and Neck cancer has been recently completed and the final results were presented*.
Disease awareness, and the opportunity
Tomuzotuximab (previously known as CetuGEX®) is a novel best-in-class immune-enhanced monoclonal antibody (mAb) against epidermal growth factor receptor (EGFR) with optimized and fully human glycosylation. There is increasing body of evidence that Tomuzotuximab may improve the clinical benefit of cancer patients indicated to receive EGFR-targeted therapy. Target indications for clinical development include squamous cell carcinoma of the head and neck (SCCHN), KRAS wild-type-expressing and KRAS mutated colorectal cancer (CRC) as well as non-small cell lung cancer (NSCLC).
In a Phase I dose escalation study, single agent Tomuzotuximab was well tolerated and showed promising therapeutic activity in patients with various solid tumors, including complete and partial responses and long lasting disease control. In April 2014, Glycotope initiated a Phase 2b study with Tomuzotuximab to treat squamous cell carcinomas of the head and neck (SCCHN). The recruitment phase for this study has recently been completed. Clinical proof of concept results are expected for mid-2017.
Differentiation/mode of actions/specificity
Due to the optimization of a series of sugar determinants, Tomuzotuximab has shown to be up to 250-fold more active in anti-tumor ADCC compared to cetuximab, in pre-clinical studies, making Tomuzotuximab highly potent for patients of all ADCC receptor allotypes and KRAS-mutant patients. This enhanced potency may increase the number of patients and indications suitable for Tomuzotuximab.