EClinicalMedicine · 2026
E7386 plus lenvatinib in patients with advanced endometrial cancer that progressed on platinum-based chemotherapy and an anti-PD-(L)1 immunotherapy: a single-arm, open-label, global phase 1b/2 dose-expansion cohort.
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Lee Jung-Yun, Hasegawa Kosei, Kim Byoung-Gie, Berman Barry, Suzuki Shiro, Corr Bradley, Yunokawa Mayu, Orr Douglas, Yamamoto Noboru, Soliman Pamela T, Miller David S, Potdar Alka A, Sahara Takatoshi, Kimura Takayuki, Dutta Lea, Wu Jincao, McKenzie Jodi, Kyi Chrisann
Аннотация
BACKGROUND: Novel therapies are needed for advanced endometrial cancer (aEC) that recurs after chemotherapy + immunotherapy. Lenvatinib has antitumour activity in patients with aEC after platinum-based chemotherapy and is approved in combination with pembrolizumab for aEC following prior systemic therapy. E7386, an oral anticancer agent, inhibits the interaction between β-catenin and CREB-binding protein (CBP). Preliminary results of a dose expansion cohort of Study 102 (n = 16) showed manageable safety and promising antitumour activity of E7386 + lenvatinib in aEC that progressed after platinum-based chemotherapy and anti-programmed cell death (ligand) 1, including responses in patients with prior lenvatinib. We report safety and antitumour activity for this complete dose expansion cohort.
METHODS: In a dose expansion cohort of Study 102 (NCT04008797), patients with aEC that progressed after platinum-based chemotherapy and immunotherapy received E7386 120 mg twice daily plus lenvatinib 14 mg once daily (amended from 20 mg during enrolment). The primary endpoint was safety; secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate, and progression-free survival by investigator per RECIST v1·1).
FINDINGS: Thirty patients were enrolled; 16 (53·3%) previously received lenvatinib. By data cut-off (4 June, 2025), five (16·7%) patients had treatment ongoing. All patients experienced treatment-emergent adverse events (TEAEs), most commonly vomiting (n = 22, 73·3%). Nineteen (63·3%) patients had grade 3 TEAEs, most frequently diarrhoea (n = 4). No grade 4-5 AEs were observed. TEAEs led to withdrawal of lenvatinib and/or E7386 in two patients. Overall, 11 patients (three with prior lenvatinib) had a confirmed response (one complete, ten partial) for an ORR of 36·7% (95% CI: 19·9-56·1). In patients without prior lenvatinib (n = 14), the ORR was 57·1% (95% CI: 28·9-82·3).
INTERPRETATION: E7386 + lenvatinib showed promising antitumour activity with a manageable safety profile in heavily pretreated patients with aEC following platinum-based chemotherapy + immunotherapy. The dose-optimisation phase of Study 102 (E7386 + lenvatinib in patients with advanced endometrial carcinoma) is currently enrolling (NCT04008797).
FUNDING: Eisai Inc., Nutley, NJ, USA.
METHODS: In a dose expansion cohort of Study 102 (NCT04008797), patients with aEC that progressed after platinum-based chemotherapy and immunotherapy received E7386 120 mg twice daily plus lenvatinib 14 mg once daily (amended from 20 mg during enrolment). The primary endpoint was safety; secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate, and progression-free survival by investigator per RECIST v1·1).
FINDINGS: Thirty patients were enrolled; 16 (53·3%) previously received lenvatinib. By data cut-off (4 June, 2025), five (16·7%) patients had treatment ongoing. All patients experienced treatment-emergent adverse events (TEAEs), most commonly vomiting (n = 22, 73·3%). Nineteen (63·3%) patients had grade 3 TEAEs, most frequently diarrhoea (n = 4). No grade 4-5 AEs were observed. TEAEs led to withdrawal of lenvatinib and/or E7386 in two patients. Overall, 11 patients (three with prior lenvatinib) had a confirmed response (one complete, ten partial) for an ORR of 36·7% (95% CI: 19·9-56·1). In patients without prior lenvatinib (n = 14), the ORR was 57·1% (95% CI: 28·9-82·3).
INTERPRETATION: E7386 + lenvatinib showed promising antitumour activity with a manageable safety profile in heavily pretreated patients with aEC following platinum-based chemotherapy + immunotherapy. The dose-optimisation phase of Study 102 (E7386 + lenvatinib in patients with advanced endometrial carcinoma) is currently enrolling (NCT04008797).
FUNDING: Eisai Inc., Nutley, NJ, USA.