Abstract 3734: Pharmacokinetics of sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC) targeting Trop-2, in patients with diverse advanced solid tumors

BACKGROUND: Sacituzumab govitecan (IMMU-132), an ADC targeting Trop-2, an antigen present in many solid tumors, uses SN-38, a topoisomerase I inhibitor that has nanomolar potency derived from irinotecan (IRI), and a pH sensitive linker that releases SN-38 gradually (in vitro, 50% released per 1 day in serum). Clinical studies in patients (pts) with diverse solid tumors have shown manageable toxicity (dose-limiting neutropenia, diarrhea but lower incidence than IRI) and encouraging efficacy. METHODS: Conjugate and IgG were monitored in pts given 8 (N = 24) or 10 mg/kg (N = 29) by ELISA. SN-38 and glucuronidated SN-38 (SN-38G) were measured by reversed-phase HPLC. SN-38 and SN-38G levels are expressed as the amount of drug dissociated from the conjugate (i.e., Free SN-38) and the amount bound to the IgG (Total SN-38). UGT1A1 status was determined in baseline blood sample from 146 pts. RESULTS: IMMU-132 cleared with a half-life of 11.7-18.9 h, depending on the assay, while the IgG half-life was 4-5 days, which agrees with in vitro drug-release data. Levels of Free SN-38 at 30 min or 1 d after injection were