Abstract CT142: The first-in-human trial of USP28 inhibitor CT1113

Abstract The deubiquitinase USP28 plays an important role in maintaining the expression levels of a large number of onco-proteins prominent among which is c-MYC. Previous work has shown the potential of USP28 as a pan-cancer therapeutic target. We identified a potent and specific inhibitor of the deubiquitinase, CT1113, which showed excellent preclinical anti-tumor activities. The inhibitor can induce c-MYC degradation in cancer cell lines with all different tissue-origins and in xenograft tumors. We therefore launched a first-in-human phase I trial of CT1113 in patients with relapsed/refractory acute myeloid leukemia (R/R AML). The compound showed excellent safety and PK profiles. Importantly, preliminary efficacy was observed, validating USP28 as a therapeutic target. A phase II trial has been planned. Citation Format: Jie Jin, Xingnong Ye, Huafeng Wang, Xiang Shen, Jin Peng, Pumin Zhang. The first-in-human trial of USP28 inhibitor CT1113 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT142.