Abstract The development of small-molecule inhibitors targeting Focal Adhesion Kinase (FAK) has been ongoing for several decades. In May 2025, the FDA approved a combination therapy involving FAK and MEK/RAF inhibitors for the treatment of low-grade serous ovarian cancer, marking a significant advancement in FAK-targeted therapies. In this study, we present IN10028, a second-generation FAK inhibitor that demonstrates enhanced efficacy in combination therapies and favorable safety profiles. IN10028 effectively targets both FAK1 and FAK2, exhibiting IC50 values of 0.2 nM and 60.1 nM, respectively, and significantly inhibits FAK-related signaling pathways. Compared to IN10018, a first-generation FAK inhibitor, IN10028 shows superior cancer cell cytotoxicity. Notably, IN10028 also demonstrates stronger target engagement than several first-generation FAK inhibitors. Through experiments conducted in animal models, IN10028 was evaluated in both monotherapy and combination therapy settings, consistently outperforming multiple first-generation FAK inhibitors in terms of tumor growth inhibition. Additionally, pharmacokinetic and toxicity studies necessary for Investigational New Drug (IND) filing have been completed, with the IND application anticipated in December 2025. Citation Format: Baoyuan Zhang, Hao Wang, Jiaming Gao, Fengmin Xi, Liyuan Liu, Leo Liu, Zaiqi Wang. IN10028, a next-generation FAK inhibitor discovered for the treatment of solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5867.
Zhang et al. (Fri,) studied this question.