Sacituzumab Govitecan ADC from Immunomedics Was Designated as Fast Track by FDA

Recently, the FDA has designated Sacituzumab Govitecan as Fast Track. Sacituzumab govitecan, also called immu-132, is one of the antibody-drug conjugates (ADCs) made by combining the humanized monoclonal antibody against hRS7 and the topological isomerase inhibitor sn-38 as the cross-linking reagent. HRS7 is a monoclonal antibody against trophoblast surface antigen (trop-2). A great number of TROP-2 are expressed on the cell surface of a variety of human tumors, such as breast cancer, cervical cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer cell surface, but this kind of antigen expression is limited in normal tissue. So hRS7 can selectively combine TROP-2, and efficiently transport the anticancer drug SN-38 to these tumor tissues. SN-38 is an effective metabolite of the standard therapy for metastatic colorectal cancer. Irinotecan is clinically used for the treatment of multiple solid tumors, but in particular, its gastrointestinal side effects limit its wider use. Sacituzumab govitecan is expected to solve these problems as a new generation of antibody drug conjugates. HRS7 combined with trop-2 can internalize into tumor cells, thus acting as a delivery tool for cytotoxic drugs. By delivering the SN-38 to the tumor targeted antibody, it theoretically increases the drug concentration in the tumor effectively, while reducing the blood concentration of cytotoxin in the circulatory system. In fact, pre-clinical studies have shown that sacituzumab govitecan was 136 times higher in the study of human pancreatic cancer than irinotecan, effectively improving the treatment effciency. In an I/II experiment (NCT01631552, abstract no. 2504), 8-12 mg/kg of sacituzumab govitecan was injected for 8-12 weeks in the first and eighth days of every three weeks. 34% patients with advanced lung cancer who have been treated 3 times in average expressed response, and a further 53% patients with small cell lung cancer and 73% of patients with non-small cell lung cancer diseases did not worsen. Sacituzumab govitecan is a special one in a new generation of antibody drug conjugates, which not only has as high as 7.6, but is also introduced a 7 polyethylene glycol to improve the water solubility of ADC and avoid the precipitation effect. What’s more special is its low activity of SN- 38, thepayload, which changes the perception of the requirements for the preparation of ADC cell activity. For example, given the limited number of ADC drug, most people in this field believe that the payload’s inhibitory activity (IC90) should be higher than 1 nM. However, the inhibitory activity of the sn-38 on most cancer cells is much lower, significantly lower than the current two listed ADCs, Adcetris and Kadcyla, and lower than the biological activity of ADC payload in clinical development stage.

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