Abstract 5638: Preclinical and clinical studies of PEP07, a novel brain penetrating Chk1 inhibitor, on solid tumor treatments

Abstract PEP07 is a potent and selective brain penetrating oral 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. PEP07 showed strong activity in repressing cancer cell growth in vitro and in vivo in different solid cancer models. Over 100 cell lines showed IC50<0.5μM toward PEP07 in vitro, and PEP07 achieved over 90% tumor growth inhibition (TGI) in multiple in vivo models either by monotherapy or combined with standard of care (SoC) treatments. With the property of blood-brain barrier (BBB) penetration, PEP07 was able to inhibit brain cancer in orthotopic models when combined with SoC treatments. In addition, in vitro cell proliferation and transcriptome data were used to train artificial neuron network (ANN) models to identify cancer cells that are sensitive to PEP07. Patient-derived tumor cells (PDCs) were used to validate the prediction of sensitive cells by ANN models. PEP07 is currently being evaluated in clinical studies for both hematologic and solid cancers. PEP07-102 (NCT05983523), a Phase 1, open-label, multi-center PK/PD and dose-escalation study employs an accelerated titration design combined with a traditional 3+3 approach assessing PEP07 as monotherapy in patients with advanced or metastatic solid tumors. Citation Format: Chieh-Fang Cheng, Hui-Ling Chen, Feng_Yu Lee, Cheng-Hao Liu, Chien-Feng Li, Hong-Ren Wang. Preclinical and clinical studies of PEP07, a novel brain penetrating Chk1 inhibitor, on solid tumor 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 5638.