Characterization of an anti-Trop-2-SN-38 antibody-drug conjugate (IMMU-132) with potent activity against solid cancers.

3107 Background: IMMU-132 is an antibody-drug conjugate (ADC) made from a humanized anti-Trop-2 mAb (hRS7) coupled through a linker to SN-38, the active metabolite of CPT-11. Trop-2 is found in a wide range of tumor, including gastric, pancreatic, triple-negative breast (TNBC), colonic, prostate, and lung. Current Phase I/II clinical trials confirm the anticancer activity of IMMU-132 in cancers expressing Trop-2. The current studies further characterize IMMU-132 in terms of conjugation, mechanism of action (MoA), and efficacy. Methods: SN-38 conjugation to hRS7 was analyzed by HIC, LC-MS, and HPLC. MoA was assessed by comparisons in binding, ADCC, and pro-apoptotic signaling pathways. Efficacy studies were performed in mice bearing human tumor xenografts. Results: IMMU-132 has a drug to antibody ratio of 7.6, <1% aggregation, and no loss in binding to cells or to a Trop-2 chip (cells: KD = 0.63 ± 0.26 nM v 0.54 ± 0.17 nM; BIACore: 0.26 ± 0.14 v 0.51 ± 0.04 nM, IMMU-132 and hRS7, respectively). Linkage che...