Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775])

A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) versus treatment of physician's choice (doxorubicin or paclitaxel) for the treatment of advanced endometrial cancer. Participants will be randomly assigned to receive either pembrolizumab and lenvatinib or treatment of physician's choice. The primary study hypothesis is that pembrolizumab in combination with lenvatinib prolongs progression free survival (PFS) and overall survival (OS) when compared to treatment of physician's choice.

Study Overview

• Status: Completed
• Conditions: Endometrial Neoplasms
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Lenvatinib; Drug: Paclitaxel; Drug: Doxorubicin

• Study Type: Interventional
• Enrollment (Actual): 827
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Instituto de Investigaciones Metabólicas
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman
  • Buenos Aires, Argentina, C1417DTB
    • Instituto de Oncología Ángel H. Roffo
  • Buenos Aires, Argentina, C1426ANZ
    • Instituto Médico Especializado Alexander Fleming
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, B1884BBF
      • Centro de Oncología e Investigación Buenos Aires COIBA
    • Mar del Plata, Buenos Aires, Argentina, B7602CBM
      • Hospital Privado de La Comunidad
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women s Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St John of God
• Brazil
  • Belo Horizonte, Brazil, 30130-100
    • Faculdade de Medicina da Universidade Federal de Minas Gerais
  • Goiás
    • Goiânia, Goiás, Brazil, 74175-120
      • Hospital Araujo Jorge
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 20220-410
      • Instituto Nacional do Cancer II
  • São Paulo
    • Jaú, São Paulo, Brazil, 17210-080
      • Fundacao Dr Amaral Carvalho
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer de Sao Paulo - ICESP
    • São Paulo, São Paulo, Brazil, 01317-000
      • Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda
• Canada
  • Québec, Canada, G1R 2J6
    • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa General Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Science Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l Universite de Montreal - CHUM
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l'Estrie-CHUS
• Colombia
  • Barranquilla, Colombia, 08002
    • Biomelab S A S
  • Bogotá, Colombia, 111321
    • Clinica Colsanitas S.A. - Sede Clinica Universitaria Colombia
  • Medellín, Colombia, 50015
    • Rodrigo Botero SAS
  • Medellín, Colombia, 50032
    • Fundacion Colombiana de Cancerologia Clinica Vida
  • Montería, Colombia, 230002
    • Oncomedica S.A.
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Clínica del Country
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundacion Valle del Lili
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Caen, France, 14076
    • Centre de Lutte Contre le Cancer François Baclesse
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Leon Berard
  • Montpellier, France, 34298
    • Institut Regional du Cancer de Montpellier - ICM
  • Nantes, France, 44277
    • Hôpital privé du Confluent
  • Paris, France, 75014
    • Groupe Hospitalier Broca Cochin Hotel Dieu
  • Paris, France, 75020
    • Hopital Diaconesses Croix Saint Simon
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
  • Plérin, France, 22190
    • Centre Armoricain de Radiotherapie Imagerie medicale et Oncologie
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany
    • EISAI Trial Site 4
  • Dresden, Germany
    • EISAI Trial Site 2
  • Erlangen, Germany
    • EISAI Trial Site 1
  • Hamburg, Germany
    • EISAI Trial Site 6
  • Rostock, Germany
    • EISAI Trial Site 3
  • Tübingen, Germany
    • EISAI Trial Site 5
• Ireland
  • Dublin, Ireland, D07 R2WY
    • Mater Misericordiae University Hospital
• Israel
  • Beersheba, Israel, 84101
    • Soroka Medical Center
  • Haifa, Israel, 3525408
    • Rambam Medical Center
  • Holon, Israel, 5822012
    • Edith Wolfson Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center. Ein Kerem
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center
• Italy
  • Catania, Italy, 95126
    • Azienda Ospedaliera per l Emergenza Cannizzaro
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Roma, Italy, 168
    • Policlinico Universitario Agostino Gemelli
• Japan
  • Kagoshima, Japan
    • EISAI Trial Site 16
  • Niigata, Japan
    • EISAI Trial Site 3
  • Tokyo, Japan
    • EISAI Trial Site 10
  • Tokyo, Japan
    • EISAI Trial Site 12
  • Tokyo, Japan
    • EISAI Trial Site 13
  • Tokyo, Japan
    • EISAI Trial Site 6
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan
      • EISAI Trial Site 9
  • Chiba
    • Kashiwa, Chiba, Japan
      • EISAI Trial Site 18
  • Ehime
    • Matsuyama, Ehime, Japan
      • EISAI Trial Site 7
    • Tōon, Ehime, Japan
      • EISAI Trial Site 15
  • Fukoka
    • Kurume, Fukoka, Japan
      • EISAI Trial Site 5
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • EISAI Trial Site 11
  • Hyōgo
    • Akashi, Hyōgo, Japan
      • EISAI Trial Site 8
  • Ibaraki
    • Tsukuba, Ibaraki, Japan
      • EISAI Trial Site 17
  • Iwate
    • Morioka, Iwate, Japan
      • EISAI Trial Site 4
  • Kanagawa
    • Isehara, Kanagawa, Japan
      • EISAI Trial Site 19
  • Miyagi
    • Sendai, Miyagi, Japan
      • EISAI Trial Site 14
  • Saitama
    • Hidaka, Saitama, Japan
      • EISAI Trial Site 1
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan
      • EISAI Trial Site 2
• Mexico
  • Mexico City, Mexico, 3310
    • Grupo Medico Camino Sc
  • Toluca, Mexico, 50080
    • Centro Hemato Oncologico Privado
  • Veracruz, Mexico, 91900
    • FAICIC S De RL De CV
  • Estado de Baja California
    • La Paz, Estado de Baja California, Mexico, 23040
      • Investigacion Onco Farmaceutica S de RL de CV
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64060
      • Alivia Clinica de Alta Especialidad S.A. de C.V.
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• Poland
  • Bielsko-Biala, Poland, 43-300
    • Beskidzkie Centrum Onkologii im. Jana Pawla II
  • Gdynia, Poland, 81-159
    • Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o.
  • Gliwice, Poland, 44-101
    • Centrum Onkologii Instytut im. Marii Sklodowskiej Curie
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki
  • Szczecin, Poland, 70-111
    • Pomorski Uniwersytet Medyczny w Szczecinie
  • Warsaw, Poland, 00-315
    • Szpital Kliniczny im Ks Anny Mazowieckiej
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-115
      • Centrum Onkologii Instytut im. Marii Sklodowskiej Curie
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie
• Russia
  • Barnaul, Russia, 656049
    • Altay Regional Oncology Dispensary
  • Kazan', Russia, 420029
    • Republican Clinical Oncology Dispensary of Tatarstan MoH
  • Moscow, Russia, 115478
    • FSBI National Medical Oncology Research Center n.a. N.N. Blokhina
  • Moscow, Russia, 115682
    • FSBI-FRCC of Special Types Med. Care & Technologies FMBA of Russia
  • Saint Petersburg, Russia, 191014
    • Leningrad Regional Oncology Center
  • Saint Petersburg, Russia, 198255
    • SPb SBHI City Clinical Oncological Dispensary
  • Saransk, Russia, 430032
    • Mordovia Republican Oncological Dispensary
  • Tomsk, Russia, 624028
    • Tomsk National Research Medical Center of Russian Academy of Sciences
  • Ufa, Russia, 450054
    • Republican Clinical Oncology Dispensary of Republic of Bashkortostan
• South Korea
  • Seoul, South Korea, 3080
    • Seoul National University Hospital
  • Seoul, South Korea, 5505
    • Asan Medical Center
  • Seoul, South Korea, 6351
    • Samsung Medical Center
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
• Spain
  • Barcelona, Spain, 8035
    • Hospital General Universitari Vall d Hebron
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital Universitario Gregorio Maranon
  • Madrid, Spain, 28027
    • Clinica Universitaria Navarra - Madrid
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe de Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 8908
      • Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals
• Taiwan
  • Kaohsiung City, Taiwan, 813
    • Kaohsiung Veterans General Hospital
  • Kaohsiung City, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F.
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan District, Taiwan, 33305
    • Chang Gung Medical Foundation. Linkou Branch
  • Beitou
    • Taipei, Beitou, Taiwan, 11217
      • Taipei Veterans General Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi
  • Ankara, Turkey (Türkiye), 06000
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06490
    • Baskent Universitesi Ankara Hastanesi
  • Bursa, Turkey (Türkiye), 16110
    • Acibadem Bursa Hastanesi
  • Istanbul, Turkey (Türkiye), 34303
    • Acibadem Universitesi Atakent Hastanesi
  • Istanbul, Turkey (Türkiye), 34349
    • Florence Nightingale Gayrettepe Hastanesi
  • Izmir, Turkey (Türkiye), 35040
    • Ege Universitesi Tip Fakultesi
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Hospital
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust - St Bartholomew s Hospital
  • London, United Kingdom, SE1 9RT
    • Guy s & St Thomas NHS Foundation Trust
  • London, United Kingdom, SM2 5PT
    • The Royal Marsden Foundation Trust
  • London, United Kingdom, WC1E 6AG
    • University College Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates, PC- HAL
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco
    • Santa Monica, California, United States, 90095
      • University of California Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale New Haven
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Health System
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Wheaton, Maryland, United States, 20902
      • Maryland Oncology Hematology, P.A.
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Med Ctr
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Gynecology Oncology
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • UT West Cancer Center
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology-South Austin
    • Dallas, Texas, United States, 75390-9032
      • University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78240
      • Texas Oncology-San Antonio Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has a histologically confirmed diagnosis of endometrial carcinoma (EC)
2. Documented evidence of advanced, recurrent or metastatic EC.

3. Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting.

   Note: There is no restriction regarding prior hormonal therapy.

4. Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.
5. Has at least 1 measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR.
6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.
7. Is not pregnant, breastfeeding, and agrees to use a highly effective method of contraception during the treatment period and for at least 120 days (for participants treated with lenvatinib plus pembrolizumab) or at least 180 days (for participants treated with treatment of physician's choice [TPC]) after the last dose of study treatment.

Exclusion Criteria:

1. Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
2. Has unstable central nervous system (CNS) metastases.
3. Has active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within 24 months of study start.
4. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
5. Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
6. Has radiographic evidence of major blood vessel invasion/infiltration.
7. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment.
8. Has a history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment.
9. Has an active infection requiring systemic treatment.
10. Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
11. Is positive for Human Immunodeficiency Virus (HIV).
12. Has active Hepatitis B or C.
13. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study start -Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years.
16. Is pregnant or breastfeeding.
17. Has had an allogenic tissue/solid organ transplant.
18. Has received >1 prior systemic chemotherapy regimen (other than adjuvant or neoadjuvant) for Endometrial Cancer. Participants may receive up to 2 regimens of platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or adjuvant treatment setting.
19. Has received prior anticancer treatment within 28 days of study start. All acute toxicities related to prior treatments must be resolved to Grade ≤1, except for alopecia and Grade ≤2 peripheral neuropathy.
20. Has received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
21. Has received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who has discontinued from that treatment due to a Grade 3 or higher immune-related adverse event.
22. Has received prior radiation therapy within 21 days of study start with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks of study start. Participants must have recovered from all radiation-related toxicities and/or complications prior to randomization.
23. Has received a live vaccine within 30 days of study start.
24. Has a known intolerance to study treatment (or any of the excipients).
25. Prior enrollment on a clinical study evaluating pembrolizumab and lenvatinib for endometrial carcinoma, regardless of treatment received.
26. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of study start.
27. Participants with urine protein ≥1 gram (g)/24 hour.
28. Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms).
29. Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib 20 mg + Pembrolizumab 200 mg; Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.	Drug: Pembrolizumab; 200 mg administered by IV infusion on Day 1 of each 21-day cycle.; Other Names: MK-3475; KEYTRUDA®; Drug: Lenvatinib; 20 mg administered orally (PO) QD during each 21-day cycle.; Other Names: LENVIMA®
Active Comparator: Treatment of Physician's Choice; Participants will receive either of the following treatments: doxorubicin 60 milligram per square meter (mg/m^2) administered by IV on Day 1 of each 21-day cycle for up to a maximum cumulative dose of 500 mg/m^2 OR paclitaxel 80 mg/m^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.	Drug: Paclitaxel; 80 mg/m^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.; Other Names: TAXOL®; Drug: Doxorubicin; 60 mg/m^2 administered by IV on Day 1 of each 21-day cycle.; Other Names: ADRIAMYCIN®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Mismatch Repair Proficient (pMMR) Participants	PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.	Up to approximately 27 months
PFS Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on BICR in All-comer Participants	PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.	Up to approximately 27 months
Overall Survival (OS) in pMMR Participants	OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the date of data cut-off were censored at the date the participant was last known alive, or date of data cut-off, whichever occurred first.	Up to approximately 43 months
OS in All-comer Participants	OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the date of data cut-off were censored at the date the participant was last known alive, or date of data cut-off, whichever occurred first.	Up to approximately 43 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib	Sparse pharmacokinetic (PK) samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted CL/F for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.	Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)
Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib	Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted AUC for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.	Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)
Objective Response Rate (ORR) in pMMR Participants	ORR was defined as the percentage of participants who had best overall response of either complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	Up to approximately 80 months
ORR in All-comer Participants	ORR was defined as the percentage of participants who had best overall response of either complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	Up to approximately 80 months
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) in pMMR Participants	EORTC QLQ-C30 was a questionnaire which included 30 questions that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.	Baseline, Week 12
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) in All-comer Participants	EORTC QLQ-C30 was a questionnaire which included 30 questions that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.	Baseline, Week 12
Number of Partricipants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Immune-Related Adverse Events (irAEs)	TEAEs were AEs that occurred (or worsened, if present at baseline) after the first dose of study drug through 28 days after the last dose. An AE was any untoward medical occurrence in a participant temporally associated with use of study treatment, whether or not related to the treatment. An SAE was any untoward medical occurrence at any dose that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly/birth defect. An irAE was any unfavorable and unintended immune-related sign, symptom, or disease (new or worsening) temporally associated with study therapy, regardless of whether a causal relationship with the therapy could be determined.	Up to approximately 77 months
Number of Participants Who Discontinued Study Treatment Due to a TEAE in pMMR Participants	TEAEs was defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to approximately 77 months
Number of Participants Who Discontinued Study Treatment Due to a TEAE in All-comer Participants	TEAEs was defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to approximately 77 months
Time to Treatment Failure Due to Toxicity in pMMR Participants	Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date a participant discontinued study treatment due to TEAEs.	Up to approximately 77 months
Time to Treatment Failure Due to Toxicity in All-comer Participants	Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date a participant discontinued study treatment due to TEAEs.	Up to approximately 77 months
Plasma Concentration of Lenvatinib Versus Time in All-comer Participants	Pharmacokinetic (PK) samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted plasma concentration of lenvatinib was then derived from the PK model.	Cycle 1 day 1 0.5-4 hours (h), 6-10 postdose; Cycle 1 day 15 predose; Cycle 1 day 15 2-12h postdose, Cycle 2 day 1 predose, 0.5-4h, 6-10 h (Each cycle is 21 days)
Plasma Concentration of Lenvatinib Versus Time in pMMR Participants	PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted plasma concentration of lenvatinib was then derived from the PK model.	Cycle 1 day 1 0.5-4 hour (h), 6-10 postdose; Cycle 1 day 15 predose; Cycle 1 day 15 2-12h postdose, Cycle 2 day 1 predose, 0.5-4h, 6-10 h (Each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Eisai Inc.

Publications and helpful links

General Publications

• Makker V, Colombo N, Casado Herraez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309-KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19.
• Yonemori K, Fujiwara K, Hasegawa K, Yunokawa M, Ushijima K, Suzuki S, Shikama A, Minobe S, Usami T, Kim JW, Kim BG, Wang PH, Chang TC, Yamamoto K, Han S, McKenzie J, Orlowski RJ, Miura T, Makker V, Man Kim Y. Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician's choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer. J Gynecol Oncol. 2024 Mar;35(2):e40. doi: 10.3802/jgo.2024.35.e40. Epub 2024 Jan 19.
• Colombo N, Lorusso D, Monk BJ, Slomovitz B, Hasegawa K, Nogueira-Rodrigues A, Zale M, Okpara CE, Barresi G, McKenzie J, Makker V. Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. Oncologist. 2024 Jan 5;29(1):25-35. doi: 10.1093/oncolo/oyad201.
• Lorusso D, Colombo N, Herraez AC, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay SE, Ray-Coquard IL, Shapira-Frommer R, Kim YM, McCormack M, Massaad R, Nguyen AM, Zhao Q, McKenzie J, Prabhu VS, Makker V. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice. Eur J Cancer. 2023 Jun;186:172-184. doi: 10.1016/j.ejca.2023.03.015. Epub 2023 Mar 23.
• Makker V, Colombo N, Casado Herraez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. doi: 10.1200/JCO.22.02152. Epub 2023 Apr 14.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): March 1, 2022
• Study Completion (Actual): February 26, 2025

Study Registration Dates

• First Submitted: April 25, 2018
• First Submitted That Met QC Criteria: April 25, 2018
• First Posted (Actual): May 7, 2018

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: paclitaxel; pembrolizumab; lenvatinib; programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1); doxorubicin; programmed cell death ligand 2 (PD-L2, PDL2); vascular endothelial growth factor (VEGF) receptors; phase 3 endometrial cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Taxoids; Cyclodecanes; Diterpenes; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Doxorubicin; Paclitaxel; pembrolizumab; lenvatinib
• Other Study ID Numbers: E7080-G000-309; 2017-004387-35 (EudraCT Number); MK3475-775 (Other Identifier: Merck Protocol Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No