525MO - Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Study 309/KEYNOTE-775

Background

The primary endpoint hypotheses for the phase 3 Study 309/KEYNOTE-775 were formally tested at interim analysis 1; LEN + pembro demonstrated statistically significant improvements in PFS and OS vs TPC in pts with aEC. ORR was higher with LEN + pembro vs TPC. We report updated analyses of this study.

Methods

Pts with aEC and 1 prior platinum-based chemotherapy regimen (up to 2 if 1 was given in the neoadjuvant/adjuvant setting) were randomized (1:1) to receive LEN 20 mg orally QD + pembro 200 mg IV Q3W or TPC (doxorubicin at 60 mg/m² IV Q3W or paclitaxel at 80 mg/m² IV QW [3 wks on; 1 wk off]). Randomization was stratified by mismatch repair (MMR) status; pts with proficient (p)MMR tumors were further stratified by ECOG PS, geographic region, and history of pelvic irradiation. We report final pre-specified OS, PFS and ORR (assessed by blinded independent central review per RECIST v1.1; in randomized pts), and safety (in pts who received treatment) (data cutoff: March 1, 2022). Analyses are descriptive.

Results

827 Pts (pMMR, n = 697; deficient MMR, n = 130) were randomized to LEN + pembro (n = 411) or TPC (n = 416). Median follow-up in all-comers was 18.7 mo (LEN + pembro) and 12.2 mo (TPC). Median PFS remained longer with LEN + pembro vs TPC in pMMR aEC (6.7 vs 3.8 mo) and in all-comers (7.3 vs 3.8 mo). Median OS remained longer with LEN + pembro vs TPC in pMMR aEC (18.0 vs 12.2 mo) and in all-comers (18.7 vs 11.9 mo) (Table), despite some pts in the TPC arm receiving subsequent LEN + pembro (pMMR, 10.0%; all-comers; 8.7%). Grade ≥ 3 TEAEs occurred in 90% of pts with LEN + pembro and 74% of pts with TPC.

Conclusions

Consistent with the primary analysis, LEN + pembro continued to demonstrate clinically meaningful improvement in PFS, OS, and ORR vs TPC in pts with aEC (pMMR and all-comers) who received prior platinum therapy. Safety was generally consistent with the primary analysis and previous studies. Table: 525MO

ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Clinical trial identification

NCT03517449.

Editorial acknowledgement

Medical writing support was provided by Irene Minkina, PhD, 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., 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

V. Makker: Financial Interests, Institutional, Funding, Study funding: Merck, Eisai, Clovis, Karyopharm, AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Non-Financial Interests, Principal Investigator: Merck; Non-Financial Interests, Advisory Role: Eisai, Clovis, Novartis, Lilly, Gsk, Karyopharm, Iteos, Faeth. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). A. Casado Herraez: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Eisai , Merck, PharmaMar; Financial Interests, Personal, Other, support for attending major international oncological conferences -virtually or face to face meetings: PharmaMar, Lilly, Roche, AstraZeneca, Merck, GSK; Financial Interests, Institutional, Research Grant: PharmaMar. B.J. Monk: Financial Interests, Personal, Other, Consultant Honoraria: Agenus, Akeso Bio, Amgen, AstraZeneca, Eisai , Elevar, Genmab/Seagen, GOG Foundation, Gradilis, ImmunoGen, Karyopharm, Iovance, Macrogenics, Mersana, Novocure, Myriad, OncoC4, Pieris, Pfizer, Puma, Regeneron, VBL, Sorrento; Financial Interests, Personal, Other, Speaker/Consultant Honoraria: Aravive, Bayer, Clovis, Roche/Genentech, Tesaro/GSK; Financial Interests, Personal, Other, Speaker/Consulant Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Principal Investigator, Consultant: Us Oncology Research. H. Mackay: Financial Interests, Personal, Advisory Board: Merck, GSK, AstraZeneca. A.D. Santin: Financial Interests, Institutional, Research Grant: Puma, Immunomedics, Gilead, Synthon, Genentech, Tesaro, Eisai; Financial Interests, Personal, Other, Personal fees: Eisai, Tesaro. D.S. Miller: Financial Interests, Personal, Advisory Role: Eisai, AstraZeneca, Karyopharm Therapeutics, Incyte, Merck Sharpe & Dohme, Asymmetric Therapeutics, Boston Biomedical Research Institute, Tarveda Therapeutics , Myriad Genetic Laboratories, GlaxoSmithKline, Abbvie, Incyte, EMD Serono, Seattle Genetics, Clinical Education Alliance, Eisai, iTEOS Therapeutics, Novocure, Novartis, Immunogen, Agenus; Financial Interests, Institutional, Research Grant: US Biotest, Advenchen Laboratories, Tesaro , Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, Merck , AstraZeneca, Millenium Pharamceuticals, Aprea AB , Regeneron, NVision, Leap Therapeutics, Novartis , Syros Pharmaceuticals , Karyopharm , Agenus , Akesobio, EMD Serono, Incyte . R.G. Moore: Financial Interests, Institutional, Research Grant: Angle plc; Financial Interests, Personal, Other, Consulting: Fujirebio Diagnostics Inc. . S.E. Baron-Hay: Financial Interests, Institutional, Research Grant: Eisai, Merck Sharpe & Dohme (Australia Pty Ltd), Pfizer; Financial Interests, Personal, Research Grant: AstraZeneca Australia; Financial Interests, Personal, Other, Honoraria: Amgen, NovartisvPharmaceuticals Australia Pty Ptd, Eli Lilly Australia, Roche, Merck Sharp and Dohme (Australia Pty Ltd). I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: Gineco. R. Shapira-Frommer: Financial Interests, Personal, Advisory Board: MSD, Neopharm; Financial Interests, Personal, Invited Speaker: MSD, BMS, Astra Zenaca, Medison, Novartis, Roche; Financial Interests, Personal, Other, consultation: Msdison; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Invited Speaker: AstraZeneca, MSD. K. Ushijima: Financial Interests, Institutional, Research Grant: MSD, Eisai. K. Yonemori: Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fujifilm Pharma, MSD, Ono; Financial Interests, Personal, Advisory Board: Novartis, Eisai , AstraZeneca, Chugai , Takeda, Genmab, OncXerna; Financial Interests, Institutional, Research Grant: MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Seagen, Haihe. E.M. Guerra Alia: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, GlaxoSmithKline, MSD, PharmaMar, Roche Posay Company. J. Huang: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. J. McKenzie: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. G. Barresi: Financial Interests, Personal and Institutional, Full or part-time Employment: MSD Austria. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest.