Randomized study evaluating optimal dose, efficacy and safety of E7386 + lenvatinib versus treatment of physicians’ choice in advanced/recurrent endometrial carcinoma previously treated with anti–PD-(L)1 immunotherapy.

TPS5632 Background: E7386 is an inhibitor of protein-protein interaction between β-catenin and CREB binding protein (CBP). E7386 + lenvatinib has demonstrated manageable safety and promising antitumor activity in the dose-expansion cohort of Study 102 that included patients with advanced endometrial cancer previously treated with immunotherapy (Lee JY et al., Ann Oncol 2024). Considering these results, we are conducting a dose-optimization part of Study 102 (NCT04008797) in patients with advanced/recurrent endometrial carcinoma (aEC). Methods: Eligible patients (≥18 years) must have a confirmed diagnosis of aEC, and prior treatment with platinum-based chemotherapy and PD-(L)1-directed therapy. Up to 3 prior lines of therapy, regardless of setting, are allowed; prior hormonal therapy and radiation do not count as lines of therapy. Patients will be randomized (1:1:1:1) to E7386 120 mg BID + lenvatinib 14 mg QD (n=30); E7386 60 mg BID + lenvatinib 14 mg QD (n=30); lenvatinib 24 mg QD monotherapy (n=30); or treatment of physician’s choice (TPC, doxorubicin 60 mg/m 2 Q3W or paclitaxel 80 mg/m 2 QW [3 weeks on/1 week off]; n=30 in total). Randomization will be stratified by region (Asia/North America/Rest of the World). The primary objective is to determine the optimal dose of E7386 + lenvatinib in aEC; additional objectives include: safety, assessing the contribution of E7386 to the overall treatment effect of E7386 + lenvatinib, and assessing the efficacy of E7386 + lenvatinib relative to TPC. Tumors will be assessed by investigators (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) every 8 weeks from the first dose. Adverse events will be monitored and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. This multinational study is actively recruiting. Clinical trial information: NCT04008797 .