Abstract 1762: Preclinical and clinical studies of PEP07, a novel brain penetrating oral Chk1 inhibitor, on AML and MCL treatments

Abstract PEP07 is an orally available and brain penetrating selective Chk1 inhibitor. Chk1 is involved in the DNA damage response and cell cycle regulation and helps maintain the integrity of the genome during cell division, especially in response to DNA damage or replication stress. Acute myeloid leukemia (AML) is characterized by an impaired DNA damage response (DDR) pathway and elevated Chk1 expression, which correlates with poor patient outcomes. Likewise, mantle cell lymphoma (MCL), a rare and aggressive form of Non-Hodgkin lymphoma, features a chromosomal translocation that leads to cyclin D1 overexpression. Since Chk1 regulates cdk1/cyclin activity, Chk1 inhibitors have been proposed as a novel therapeutic approach in this cancer. In addition to in vitro inhibitory effect on multiple hematology cancer cell lines, PEP07 has been demonstrated as monotherapy to show tumor growth inhibition and tumor regression in the AML and MCL xenograft models, respectively. It also showed enhanced tumor growth inhibition in the cytarabine-resistant AML xenograft model when combined with cytarabine. PEP07 is currently being evaluated in clinical studies for both hematologic and solid cancers. PEP07-101 (NCT05659732), a Phase 1b, open-label, multi-center PK/PD and dose-escalating study, employs an accelerated titration design combined with a traditional 3+3 approach. This study is ongoing in multiple countries and evaluates oral PEP07 as monotherapy for AML and MCL. With its ability to penetrate the blood-brain barrier (BBB), PEP07 is also being considered for investigating treatment options for brain cancer in clinical settings. Citation Format: Hui-Ling Chen, Chieh-Fang Cheng, Feng-Yu Lee, Cheng-Hao Liu, Hong-Ren Wang. Preclinical and clinical studies of PEP07, a novel brain penetrating oral Chk1 inhibitor, on AML and MCL treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1762.