Sacituzumab govitecan (IMMU-132), a next generation antibody-drug conjugate designed by Immunomedics Inc, is a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer for targeted therapy of solid cancers, was created by site-specifically conjugating a TROP-2-targeting antibody with a drug to antibody ratio of 7.6 (which is about twice that of other antibody-drug conjugates) of the moderately toxic drug, SN-38, the active metabolite of irinotecan, using a pH sensitive linker.
TROP-2 is a receptor found on many human cancer cells, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. In an animal model of human pancreatic cancer, sacituzumab govitecan delivered up to 135-times the amount of the moderately-toxic drug SN-38 to the tumor than when irinotecan, the parent drug of SN-38, was given.
With the use of a moderately-toxic drug, patients were able to tolerate a dosing schedule of once a week for two weeks followed by one week of rest in a 3-week cycle, which increases the therapeutic index of the ADC. Sacituzumab govitecan has further demonstrated activity in other solid tumors, producing partial response in patients with colorectal, esophageal, small-cell and non- small-cell lung, and urinary bladder cancers. Despite repeated dosing, so far, no antibodies against sacituzumab govitecan, either to the antibody or to the SN-38, have been detected.
Editorial Review: March 16, 2015
Last Editorial Review: November 14, 2016