738P - Global, phase Ib dose-expansion cohort of E7386 + lenvatinib (LEN) in patients (pts) with advanced (a) endometrial cancer (EC) that progressed on platinum-based chemotherapy (CTx) and an anti-PD-(L)1 immunotherapy (IO)

Background

There is a growing need for effective therapy for aEC that recurs after CTx and IO. LEN + pembrolizumab is an approved therapy for pts with aEC after systemic therapy in any setting. E7386 is a novel oral anticancer agent that modulates Wnt/β-catenin signaling by inhibiting β-catenin binding to CBP. Preclinically, E7386 enhanced antitumor activity of LEN. The open-label, phase 1b Study 102 evaluated E7386 + LEN in pts with solid tumors to determine the recommended dose for the expansion part. We report the safety and preliminary antitumor activity of an expansion cohort of pts with aEC following platinum-based CTx and an anti-PD-(L)1 IO.

Methods

Eligible pts with aEC that progressed after platinum-based CTx and an anti-PD-(L)1 IO (unless ineligible for IO) received E7386 120 mg BID + LEN 20 mg QD (changed to 14 mg during enrollment per protocol amendment). Prior LEN was allowed unless the pt discontinued (DCed) due to toxicity. Safety was a primary endpoint; secondary endpoints included ORR, duration of response (DOR), clinical benefit rate (CBR), and PFS. Responses were evaluated by investigators per RECIST v1.1.

Results

16 Pts were enrolled; 10 previously received LEN, all previously received an anti-PD-(L)1 IO. By data cutoff (Mar 7, 2024), 8 pts continued treatment; 8 DCed, mostly due to disease progression (n=4). 15 Pts had treatment-related (TR) AEs, most commonly vomiting (n=9; grade ≥3 n=1). 7 Pts had grade ≥3 TRAEs, most commonly diarrhea/proteinuria (n=2 each). There were no grade 5 AEs observed. Overall, 3 of the 16 pts treated had no postbaseline tumor assessment as of data cutoff, and 5 pts (none with prior LEN) had a confirmed partial response (PR) for an ORR of 31%. Additional data are in the table.

Conclusions

E7386 + LEN has shown promising preliminary antitumor activity with a manageable safety profile. Enrollment to the expansion part of Study 102 is ongoing. Table: 738P

aNone had received LEN as prior therapy.

bPR was not confirmed at time of data cutoff.

cthe 2 pts with unconfirmed PR were counted as SD.

dcomplete response + PR + SD for ≥23 wks. NE, not estimable.

Clinical trial identification

NCT04008797.

Editorial acknowledgement

Medical writing support was provided by Michael Venditto, PharmD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Eisai Inc.

Funding

Eisai Inc.

Disclosure

J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: BeiGene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: Ono, Takeda. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai, Sanofi, GSK; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai, Takeda. B.R. Corr: Financial Interests, Institutional, Advisory Board: GSK, Gilead, ImmunoGen, Zentalis, Merck, Corcept, ImVax; Financial Interests, Institutional, Invited Speaker: Targeted Oncology; Financial Interests, Institutional, Coordinating PI: ImmunoGen, Clovis. S. Kondo: Financial Interests, Personal, Speaker’s Bureau: Chugai, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Research Grant: AbbVie, Astellas, Daiichi Sankyo, MSD, AstraZeneca, Eisai. S. Suzuki: Financial Interests, Personal, Invited Speaker: Eisai Co Ltd, MSD K.K. M. Yunokawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Taiho, Eizai, Takeda, Mochida Pharmaceutical Co., Ltd., Merck & Co., Inc, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Advisory Board: Genmab, GSK. D.S. Miller: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Eisai Europe Limited; Financial Interests, Institutional, Member of Board of Directors: NRG Oncology; Financial Interests, Institutional, Coordinating PI: Advenchen Laboratories, Aeterna Zentaris; Financial Interests, Institutional, Local PI: Merck Sharp & Dohme, NVision, Novartis, Syros Pharmaceuticals, Karyopharm Therapeutics, Agenus, Akesobio, Leap Therapeutics. T. Tamai, L. Dutta, K. O'Hara, T. Sahara: Financial Interests, Personal, Full or part-time Employment: Eisai. V. Makker: Financial Interests, Institutional, Funding, Study funding: Merck, Eisai, Clovis, Karyopharm, AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Financial Interests, Institutional, Funding, Study Support: BMS, Duality, Faeth, Takeda; Financial Interests, Institutional, Local PI: Cullinan; Non-Financial Interests, Principal Investigator: Merck; Non-Financial Interests, Advisory Role: Eisai, Clovis, Novartis, Lilly, GSK, Karyopharm, Iteos, Faeth, Duality, Zymeworks, Morphosys, Moreo; Other, Travel to Scientific Congress-SGO2024: AstraZeneca. All other authors have declared no conflicts of interest.