39MO - Phase III ENGOT-En9/LEAP-001 study: Lenvatinib + pembrolizumab (LEN/PEMBRO) vs chemotherapy (chemo) as first-line (1L) therapy for advanced or recurrent endometrial cancer

Background

LEN/PEMBRO following prior systemic therapy in any setting, including neo/adjuvant, is a standard of care for advanced endometrial cancer (EC). The phase 3 ENGOT-en9/LEAP-001 trial (NCT03884101) compared 1L LEN/PEMBRO vs chemo in patients (pts) with advanced/recurrent EC.

Methods

Eligible pts had stage III–IV or recurrent, measurable/non-measurable, radiographically apparent EC, with no prior chemo or PD ≥6 mo after neo/adjuvant platinum-based chemo. Pts were randomized 1:1 (stratified by proficient vs deficient mismatch repair status [pMMR/dMMR] and, in the pMMR stratum, by ECOG PS [0/1], measurable disease [yes/no], and chemo/chemoradiation [yes/no]) to lenvatinib 20 mg QD plus pembrolizumab 200 mg Q3W or paclitaxel 175 mg/m² Q3W plus carboplatin AUC 6 Q3W. Dual primary endpoints were PFS (RECIST v1.1, blinded independent central review) and OS in the pMMR population and among all-comers. Secondary endpoints included ORR and safety; duration of response (DOR) was an exploratory endpoint; and efficacy outcomes assessed by tumor histology was a prespecified exploratory analysis.

Results

842 pts were randomized. At final analysis (data cutoff, 2 Oct 2023), after median follow-up of 38.4 (range, 30.3–52.9) mo, statistical significance for noninferiority (NI) OS endpoint was not achieved for LEN/PEMBRO vs chemo in the pMMR population (HR, 1.02 [95% CI, 0.83–1.26]; NI P = 0.2459875; Table). PFS and OS results for LEN/PEMBRO vs chemo by histological subtype will be presented for the pMMR population and all-comers. Treatment-related AEs occurred in 411/420 (97.9%) vs 398/411 (96.8%) treated pts in the LEN/PEMBRO vs chemo groups.Table: 39MO

^a1-sided NI P = 0.2459875 (nonsignificant), not crossing prespecified OS NI boundary, P = 0.0158890, so no further statistical testing of efficacy endpoints was performed per prespecified multiplicity strategy for type 1 error control.

Conclusions

The prespecified statistical criteria for OS and PFS in pts with pMMR IL advanced/recurrent EC were not met. Subgroup analyses identifying pts who may benefit most from LEN/PEMBRO will be presented. The safety profile was manageable and consistent with prior experience.

Clinical trial identification

NCT03884101.

Editorial acknowledgment

Medical writing assistance was provided by Sonia Mohinta, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Nutley, NJ, USA and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Eisai Inc., Nutley, NJ, USA and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

S. Pignata: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Clovis, GSK, PharmaMar; Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AstraZeneca. C. Marth: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche Austria, Novartis, MSD, PharmaMar, GSK, Pfizer, ImmunoGen, Daiichi Sankyo, Biontech, Novocure, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, GSK, Novartis, MSD, PharmaMar, Roche, AstraZeneca, GSK; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. R.G. Moore: Financial Interests, Personal, Other, Consultant: Fujirebio Diagnostics Inc. . M.J. Rubio Pérez: Financial Interests, Personal, Advisory Board, Consulting/Advisory Board: MSD, AstraZeneca, GSK, PharmaMar, Roche. M. Hall: Financial Interests, Personal, Advisory Board, Ad boards. speaker engagements: GSK; Financial Interests, Personal, Advisory Board, Ad boards: Amgen; Financial Interests, Personal, Advisory Board, Ad Boards: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad Boards, speaker engagement: Clovis Oncology; Financial Interests, Institutional, Research Grant, Funding and drug for CeNtuRIOn clinical trial - Glasgow Clinical trials Unit: Clovis Oncology; Financial Interests, Institutional, Research Grant, Research funding and drugs for CeNtuRIOn clinical trial - Glasgow Clinical Trials Unit: BMS; Financial Interests, Institutional, Research Grant, Research Funding and drug for CoRinTh clinical trial - Cardiff clinical trials Unit: Merck. C. Vulsteke: Financial Interests, Personal, Advisory Board: MSD, Janssen Cilag, GSK, Astellas Pharma, BMS, Leo Pharma, Bayer, AstraZeneca, Pfizer, Merck; Financial Interests, Institutional, Research Grant, Funding for research project on immune related toxicities: MSD. I. Braicu: Financial Interests, Personal, Research Grant, Funded Research: EU, DLR, AstraZeneca, Roche Diagnostics, Bayer; Financial Interests, Personal, Other, Honoraria/Expenses: Roche, Merck, AstraZeneca, Tesaro, GSK, CLOVIS, Roche Diagnostics, Molecular Health, EISAI; Financial Interests, Personal, Invited Speaker, Consulting/Advisory Board: Roche, Eisai, Merck, AstraZeneca, GSK, Clovis. S. Frentzas: Financial Interests, Personal, Advisory Board, Consulting/Advisory Board: Akesobio. J. McKenzie: Financial Interests, Personal, Full or part-time Employment, Full time employee of Eisai Inc.: Eisai Inc. L. Yao: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. V. Khemka: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. L. Gilbert: Financial Interests, Institutional, Research Grant, Institutional Grant: AstraZeneca, Pfizer, Merck Sharp & Dohme, Karyopharm, Tesaro, IMV, Alkermes, Clovis, ImmunoGen Inc, Roche, Mersana, Esperas, Novocure GmbH, OncoQuest Pharmaceuticals; Financial Interests, Institutional, Advisory Board: AstraZeneca, GSK, Eisai, Eisai-Merck, Alkermes. 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, Invited Speaker: Cullinan; Non-Financial Interests, Personal, Principal Investigator: Merck; Non-Financial Interests, Personal, Advisory Role: Eisai, Clovis, Novartis, Lilly, GSK, Karyopharm, Iteos, Faeth, Duality, ZYmeworks, Morphosys, Moreo; Other, Personal, Other, Travel to Scientific Congress-SGO2024: AstraZeneca. All other authors have declared no conflicts of interest.