Abstract Background: E7386 is an inhibitor of the protein-protein interaction between CREB-binding protein (CBP) and β-catenin. Currently, a clinical study of E7386 in combination with lenvatinib (LEN), a multiple receptor tyrosine kinase inhibitor mainly targeting VEGFRs and FGFRs, is ongoing for the treatment of advanced solid tumors including endometrial carcinoma (EC) (NCT04008797). We previously reported that E7386 in combination with LEN showed greater antitumor activity and reduction of tumor microvessels than each agent alone in preclinical hepatocellular carcinoma tumor models. In this study, we investigated the antitumor and antiangiogenic activities of E7386 plus LEN in multiple human EC xenograft models. Methods: Human EC cell lines (HEC151, HEC251, JHUEM2, and HEC50B) were subcutaneously inoculated into female nude mice. Mice with EC xenograft tumors were treated with E7386 at 6.25-50 mg/kg (orally PO, once daily QD) and/or LEN at 10 mg/kg (PO, QD) for 7-14 days. Tumor microvessel analysis of formalin-fixed and paraffin-embedded tumor samples was performed by immunohistochemistry staining using the anti-CD31 antibody. Results: E7386 in combination with LEN showed enhanced antitumor activity compared with either monotherapy alone without severe body weight loss (20% body weight loss) in all EC xenograft models tested. Notably, tumor regression was observed by the combination treatment in HEC251 and HEC50B models. The enhancement of antitumor activity was consistently observed across models with E7386 doses at 25 and 50 mg/kg. Tumor microvessel analysis in the HEC151 model revealed that LEN monotherapy decreased the microvessel density, and the combination treatment showed more potent antiangiogenic activity compared with LEN monotherapy. Conclusion: These results suggest that the combination of E7386 with LEN exerted enhanced antiangiogenic activity against tumor microvessels compared with LEN-alone, and demonstrated potent antitumor activity in preclinical EC xenograft models. Citation Format: Yusuke Adachi, Yudai Narita, Shogo Yamaguchi, Taro Semba, . Antitumor and antiangiogenic activities of E7386 in combination with lenvatinib in human endometrial carcinoma xenograft models 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 7171.
Adachi et al. (Fri,) studied this question.