E7386 (β-catenin–CBP inhibitor) + lenvatinib delivers 36.7% ORR in post–chemo/PD-(L)1 advanced endometrial cancer

E7386 is an oral inhibitor of the beta-catenin/CBP interaction, combined with the multikinase VEGFR/FGFR inhibitor lenvatinib in the global Phase 1b/2 Study 102 dose-expansion cohort (NCT04008797). All 30 patients with advanced endometrial cancer had progressed after platinum chemotherapy and anti-PD-(L)1 therapy; 16 had received lenvatinib previously. At the June 4, 2025 data cutoff, confirmed ORR was 36.7% overall (1 CR, 10 PR; 95% CI 19.9–56.1), but 57.1% in lenvatinib-naive patients (8/14) versus 18.8% in previously treated patients (3/16). The full paper reports median DOR of 9.1 months and median PFS of 5.5 months overall; median PFS was 10.8 months in the lenvatinib-naive group versus 4.4 months after prior lenvatinib. These subgroups should not be treated as one post-lenvatinib/pembrolizumab population. All patients had TEAEs; 63.3% had grade 3 events, most commonly grade 3 diarrhea (13.3%), with no grade 4–5 TEAEs. Two patients discontinued study drugs because of TEAEs, but dose interruptions (80.0%) and reductions (63.3%) were common. KEYNOTE-775 provides context for lenvatinib-pembrolizumab, but its pre-PD-(L)1 population is not a direct efficacy comparator.