Toxicokinetics of TBI302 in Cynomolgus Monkeys: A Hemoglobin-Floxuridine Conjugate for Treatment of Liver Cancer

摘要

Hepatocellular carcinoma (primary liver cancer) is the second most common cause of death from cancer worldwide. Floxuridine (FUdR) is an anti-cancer drug that has been used in liver cancer patients with a well characterized mechanism of action. However, systemic toxicities associated with free FUdR limit its use. TBI 302 is a hemoglobin (Hb)-FUdR conjugate that takes advantage of the body's natural mechanism of clearing cell-free Hb through the liver to selectively improve the delivery of FUdR to liver-localized tumors, while preserving FUdR activity. A GLP-compliant repeat dose toxicology study of TBI 302 was conducted in cynomolgus monkeys with the product administered by 1-hour intravenous (IV) infusion once per week for eight weeks, which included a toxicokinetic assessment.