Identification and development of biomarkers to predict the therapeutic response to the therapeutic anti-CLDN18.2-antibody IMAB362

Identification and development of biomarkers to predict the therapeutic response to the therapeutic anti-CLDN18.2-antibody IMAB362

Monoclonal antibodies, which are characterized by their high specificity and targeted mode of action, are becoming increasingly important in the treatment of cancer. These highly specific antibodies are based on a clear discrimination between tumor cells and healthy cells that enable the identification of an appropriate tumor-selective target structure. The business model of Ganymed Pharmaceuticals AG is based on the generation of "ideal antibodies" that address highly tumor-selective and novel targets. This concept was successfully implemented with the clinical development of the chimeric monoclonal IgG1 antibody IMAB362 for the treatment of gastric and esophageal cancer. IMAB362 targets CLDN18.2, a gastric differentiation gene which is found exclusively on short-lived differentiated epithelial cells of the stomach and in 70% of gastric carcinomas, as well as in other tumors. The antibody’s clinical activity and good tolerability were demonstrated in Phase I and early Phase II clinical trials, during which IMAB362 was administered as a monotherapy in single and/or multiple doses.

An important success factor for marketing authorization of IMAB362 to treat gastro-esophageal cancer is identifying those patient sub-populations that actually benefit from treatment with the drug. For this purpose, an ancillary clinical program will be established for the planned randomized Phase II trial of IMAB362, which includes a comprehensive analysis of potential predictive biomarkers associated with gastro-esophageal tumors. This includes investigating various factors that are relevant immunologically and with regard to stomach cancer, and establishing appropriate research methods for their quantification, detection and analysis. In a Phase II trial, potential predictive biomarkers, surrogate markers or PK/functionality markers are analyzed in patients with stomach cancer who were treated with IMAB362. After correlation studies, this program aims to identify a set of predictive biomarker candidates with clinical relevance which are specifically tailored to gastric cancer patients and which allow predictions to be made about the therapeutic success of IMAB362. These markers can then be used directly in a larger pivotal trial to stratify the responder population.

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