E7386 study 102: Global dose-expansion cohort of E7386 + lenvatinib (LEN) in patients (pts) with advanced endometrial cancer (aEC) that progressed on platinum-based chemotherapy (chemo) and an anti-PD-(L)1 immunotherapy (IO).

5599 Background: There is a need for novel therapies for aEC that recurs after chemo and IO. LEN has antitumor activity in pts with aEC after platinum-based chemo [Vergote 2020] and is approved in combination with pembrolizumab for aEC following prior systemic therapy. E7386 is a novel oral anticancer agent that inhibits the interaction between β-catenin and CREB-binding protein. Study 102 evaluates E7386 + LEN in pts with solid tumors including aEC. A preliminary analysis of Study 102 (n=16) showed manageable safety and promising antitumor activity in aEC that progressed after platinum-based chemo and anti-PD-(L)1, including responses in pts with prior LEN. We report safety and antitumor activity for the complete dose expansion cohort (n=30) of pts with aEC. Methods: Pts with aEC that progressed after platinum-based chemo and IO received E7386 120 mg BID + LEN 14 mg QD (amended from 20 mg during enrollment). The primary endpoint was safety; secondary endpoints included ORR, duration of response (DOR), clinical benefit rate (CBR), and PFS by investigator per RECIST v1.1. Results: 30 pts were enrolled; 16 (53.3%) previously received LEN. By data cutoff (Oct 22, 2024), 9 (30.0%) pts had treatment ongoing. 29 (96.7%) Pts had treatment-related adverse events (TRAEs), most commonly vomiting (n=21, 70.0%). 12 (40.0%) Pts had grade 3 TRAEs, most commonly nausea/proteinuria/diarrhea/hypertension/anemia (n=2 each, 6.7%). No grade 4-5 AEs were observed. TRAEs led to study drug withdrawal of LEN and E7386 in 1 patient. Overall, 9 pts (3 with prior LEN) had a confirmed response (1 complete and 8 partial) for an ORR of 30.0%. In pts without prior LEN (n=14), the ORR was 42.9%. Additional data are in the Table. Conclusions: E7386 + LEN showed promising antitumor activity with a manageable safety profile in heavily pretreated pts with aEC following platinum-based chemo and IO. The dose-optimization phase of Study 102 for E7386 + LEN in pts with aEC is currently enrolling pts ( NCT04008797 ). Clinical trial information: NCT04008797 . Age, median, yrs (range) 62.0 (36–76) 1 / 2 / 3 prior lines of therapy, n (%) 4 (13.3) / 16 (53.3) / 10 (33.3) Endometrioid / serous / clear cell / other histology, n (%) 16 (53.3) / 3 (10.0) / 2 (6.7) / 9 (30.0) Mismatch repair proficient / deficient / NA a , n (%) b 16 (53.3) / 6 (20.0) / 8 (26.7) TP53 w ild type/ mutation, n (%) c 16 (53.3) / 14 (46.7) Serious TRAEs, n (%) 7 (23.3) ORR / CBR d , % (95% CI) 30.0 (14.7–49.4) / 46.7 (28.3–65.7) SD, n (%) 12 (40.0) DOR, median, mos (95% CI) 8.0 (3.7–9.5) PFS, median, mos (95% CI) 5.3 (3.0–8.9) a Microsatellite instability-low (n=3); unknown (n=4); NA (n=1); b as reported by sites; c circulating tumor DNA analyses were conducted using plasma samples collected at baseline, and were annotated using OncoKB database to identify mutations in TP53 ; d complete response + partial response + stable disease ≥23 wks. NA, not available.