Sacituzumab govitecan

Drug Overview

Sacituzumab govitecan (Immunomedics) is an antibody-drug conjugate consisting of an anti-troponin (Trop)-2 antibody conjugated to SN-38. Trop-1 and Trop-2 are type I membrane proteins expressed in human epithelial cells at various stages of differentiation. Trop-1 and Trop-2 are located at contact sites between adjacent cells, where they bind to each other and take part in the formation of specialized cell-cell adhesion structures. Overexpression of Trop-2 has been demonstrated to be necessary and sufficient to stimulate tumor growth. Expression of Trop-1 and Trop-2 is associated with poor prognosis of several human cancers, including oral, pancreatic, gastric, ovarian, colorectal, breast, and lung tumors.

SN-38 is the active metabolite of irinotecan, an analog of camptothecin. SN-38 prevents DNA from unwinding by inhibition of topoisomerase I. SN-38 is moderately toxic, allowing it to be conjugated at a drug-to-antibody ratio (DAR) of 7.6:1, which is approximately twice the DAR of other antibody-drug conjugates. Following the binding to Trop-2, the antibody-drug conjugate is internalized into the cell where it releases SN-38, thus delivering a concentrated dose of SN-38 to the tumor.