The antibody-drug conjugate carcinoembryonic antigen-related cell adhesion molecule 5-targeting:tusamitamab ravtansine
Carcinoembryonic antigen-related cell adhesion molecule 5(CEACAM5),a cell surface glycoprotein linked to membranes by glycosylphosphatidylinositol(GPI),is lowly expressed in normal tissues but highly expressed in a variety of tumor tissues,especially in non-small-cell lung,gastrointestinal cancers,colorectal cancers,pancreatic cancer,and breast cancer.Tusamitamab ravtansine(research code:SAR408701),the fastest progressing first-in-class antibody-drug conjugate(ADC)targeting CEACAM5 is currently in Phase III clinical trials.Preclinical studies and multiple clinical trials have confirmed the promising antitumor activity and safety profile of tusamitamab ravtansine,either as monotherapy or in combination with other agents,in patients with CEACAM5-expressing non-small cell lung cancer,gastrointestinal cancers,colorectal cancers,pancreatic cancers and breast cancers.Although the interim analysis of the phase III clinical trial of tusamitamab ravtansine did not meet the primary endpoint of progression-free survival,there was an improvement trend in overall survival.Moreover,its combination with standard first-line treatment regimens showed promising antitumor activity and safety,indicating the poten-tial application of tusamitamab ravtansine in patients with CEACAM5-high expressing tumors.This article provides an over-view of the basic information,mechanism of action,preclinical studies,and clinical studies of tusamitamab ravtansine.
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