PRO1102 is an antibody-drug conjugate (ADC) directed toward HER2, a validated protein target that is overexpressed in multiple cancers, including breast and gastrointestinal cancer. PRO1102 is comprised of 1) trastuzumab, a clinically and commercially validated HER2-directed antibody, 2) a cleavable, hydrophilic linker, and 3) exatecan, a topoisomerase 1 inhibitor. The mechanism of action and the clinical potential of PRO1102 was evaluated in a series of experiments. PRO1102 maintained the same binding attributes of the parent antibody, trastuzumab, in vitro. In mouse xenograft studies, PRO1102 demonstrated robust anti-tumor activity across multiple HER2-expressing cell lines that was generally better than ADCs with alternative drug-linker technologies, such as those associated with monomethyl auristatin E, mertansine (DM1) and deruxtecan. In addition, PRO1102 retained activity in cancer cells with moderate and low HER2 expression, suggesting the potential to benefit a broader range of patients of HER2-expressing cancers. The pharmacokinetics of PRO1102 was evaluated in rats and PRO1102 was stable in circulation with disposition similar to the parent antibody. Tolerability was evaluated in mice and at PRO1102 dose levels associated with robust anti-tumor activity, PRO1102 was well tolerated. PRO1102 exhibits the attributes needed for an effective ADC with robust activity in a broad selection of HER2-expressing cancers.

Citation Format: Lei Wang, Haidong Liu, Xiao Shang, Tae H. Han, Baiteng Zhao. The preclinical pharmacology of PRO1102, a novel exatecan-based HER2-directed antibody-drug conjugate with robust anti-tumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1758.