Randomized study evaluating optimal dose, efficacy, and safety of E7386 plus lenvatinib versus treatment of physician’s choice in advanced/recurrent endometrial carcinoma previously treated with platinum-based chemotherapy and immune checkpoint inhibitors

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BACKGROUND: Randomized controlled trial data for patients with endometrial cancer who experience disease progression after anti-programmed cell death [ligand] 1 (PD-[L]1) therapy are lacking. E7386, a novel small-molecule inhibitor, has been shown to enhance anti-angiogenesis when combined with lenvatinib. The escalation and expansion parts of Study 102 showed preliminary anti-tumor activity and manageable safety of E7386 plus lenvatinib in patients with advanced, un-resectable, or recurrent endometrial cancer previously treated with anti-PD-(L)1. PRIMARY OBJECTIVE: This study aimed to determine the optimal dose of E7386 in combination with lenvatinib. STUDY HYPOTHESIS: E7386 plus lenvatinib will show a manageable safety profile and clinically meaningful anti-tumor activity in patients with advanced, un-resectable, or recurrent endometrial carcinoma previously treated with chemotherapy and anti-PD-(L)1 therapy. TRIAL DESIGN: once weekly [3 weeks on/1 week off]). MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients are aged ≥18 years with Eastern Cooperative Oncology Group performance status of 0 to 1 and must have advanced, un-resectable, or recurrent endometrial carcinoma that has progressed on/after prior platinum-based chemotherapy and PD-(L)1-directed therapy. Up to 3 previous lines of therapy are permitted. Individuals with prior treatment with lenvatinib or E7386 or known intolerance and/or known hypersensitivity to E7386, lenvatinib, doxorubicin, or paclitaxel, or any of their excipients, are not eligible to participate. PRIMARY END POINTS: The primary end points are safety and the objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator assessment at week 24. SAMPLE SIZE: The study aims to include 120 patients across approximately 80 investigational sites in North America, Europe, and Asia-Pacific regions. Estimated Dates for Completing Accrual and Presenting Results: Enrollment is expected to take approximately 9 months, with presentation of results in 2026. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, NCT04008797.