AzTrials
AzTrials

Endometrial NeoplasmsPhase 3NCT03517449

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 Phase 3 study testing Pembrolizumab, Lenvatinib and Paclitaxel in people with Endometrial Neoplasms, run by Eisai Inc. at 169 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Endometrial Neoplasms
What is being tested?
Pembrolizumab, Lenvatinib and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
827 participants
Where
169 sitesin 21 countries
Study dates
11 Jun 2018to 26 Feb 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a histologically confirmed diagnosis of endometrial carcinoma (EC)
  • Documented evidence of advanced, recurrent or metastatic EC.
  • 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.
  • Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.
  • 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.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.
  • 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.

Who cannot join

  • Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
  • Has unstable central nervous system (CNS) metastases.
  • 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.
  • Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
  • Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
  • Has radiographic evidence of major blood vessel invasion/infiltration.
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  • Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment.
  • 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.
  • Has an active infection requiring systemic treatment.
  • Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
  • Is positive for Human Immunodeficiency Virus (HIV).
  • Has active Hepatitis B or C.
  • Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • 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.
  • Is pregnant or breastfeeding.
  • Has had an allogenic tissue/solid organ transplant.
  • 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.
  • 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.
  • Has received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • 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.
  • 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.
  • Has received a live vaccine within 30 days of study start.
  • Has a known intolerance to study treatment (or any of the excipients).
  • Prior enrollment on a clinical study evaluating pembrolizumab and lenvatinib for endometrial carcinoma, regardless of treatment received.
  • 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.
  • Participants with urine protein ≥1 gram (g)/24 hour.
  • Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms).
  • Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

Trial locations and contacts

169 sites in 21 countries.

169 sites in 21 countries

United States25 sites

  • Georgia Cancer Center at Augusta University

    Augusta, Georgia, 30912

  • Texas Oncology-South Austin

    Austin, Texas, 78745

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75390-9032

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Willamette Valley Cancer Institute and Research Center

    Eugene, Oregon, 97401

  • North Shore University Health System

    Evanston, Illinois, 60201

  • UT West Cancer Center

    Germantown, Tennessee, 38138

  • John Theurer Cancer Center at Hackensack University Med Ctr

    Hackensack, New Jersey, 07601

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Miami Health System

    Miami, Florida, 33136

  • Smilow Cancer Hospital at Yale New Haven

    New Haven, Connecticut, 06510

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10022

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

  • Arizona Oncology Associates, PC- HAL

    Phoenix, Arizona, 85016

  • University of Rochester

    Rochester, New York, 14642

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • Texas Oncology-San Antonio Medical Center

    San Antonio, Texas, 78240

  • University of California San Francisco

    San Francisco, California, 94158

  • University of California Los Angeles

    Santa Monica, California, 90095

  • Sanford Gynecology Oncology

    Sioux Falls, South Dakota, 57104

  • Holy Name Medical Center

    Teaneck, New Jersey, 07666

  • Maryland Oncology Hematology, P.A.

    Wheaton, Maryland, 20902

Other trials in United States

Japan19 sites

  • EISAI Trial Site 8

    Akashi, Hyōgo

  • EISAI Trial Site 1

    Hidaka, Saitama

  • EISAI Trial Site 19

    Isehara, Kanagawa

  • EISAI Trial Site 16

    Kagoshima

  • EISAI Trial Site 18

    Kashiwa, Chiba

  • EISAI Trial Site 5

    Kurume, Fukoka

  • EISAI Trial Site 7

    Matsuyama, Ehime

  • EISAI Trial Site 4

    Morioka, Iwate

  • EISAI Trial Site 9

    Nagoya, Aichi-ken

  • EISAI Trial Site 3

    Niigata

  • EISAI Trial Site 11

    Sapporo, Hokkaido

  • EISAI Trial Site 14

    Sendai, Miyagi

  • EISAI Trial Site 2

    Sunto-gun, Shizuoka

  • EISAI Trial Site 10

    Tokyo

  • EISAI Trial Site 12

    Tokyo

  • EISAI Trial Site 13

    Tokyo

  • EISAI Trial Site 6

    Tokyo

  • EISAI Trial Site 15

    Tōon, Ehime

  • EISAI Trial Site 17

    Tsukuba, Ibaraki

Other trials in Japan

France12 sites

  • Institut Bergonie

    Bordeaux, 33076

  • Centre de Lutte Contre le Cancer Francois Baclesse

    Caen, 14076

  • Centre Oscar Lambret

    Lille, 59020

  • Centre Leon Berard

    Lyon, 69008

  • Institut Regional du Cancer de Montpellier - ICM

    Montpellier, 34298

  • Hopital prive du Confluent

    Nantes, 44277

  • Groupe Hospitalier Broca Cochin Hotel Dieu

    Paris, 75014

  • Hopital Diaconesses Croix Saint Simon

    Paris, 75020

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69310

  • Centre Armoricain de Radiotherapie Imagerie medicale et Oncologie

    Plérin, 22190

  • Centre Eugene Marquis

    Rennes, 35042

  • Institut Gustave Roussy

    Villejuif, 94800

Other trials in France

Canada11 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • Centre Hospitalier de l Universite de Montreal - CHUM

    Montreal, Quebec, H2X 3E4

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa General Hospital

    Ottawa, Ontario, K1H 8L6

  • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec

    Québec, G1R 2J6

  • CIUSSS de l'Estrie-CHUS

    Sherbrooke, Quebec, J1H 5N4

  • Sunnybrook Health Science Centre

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

  • Cancer Care Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Russia9 sites

  • Altay Regional Oncology Dispensary

    Barnaul, 656049

  • Republican Clinical Oncology Dispensary of Tatarstan MoH

    Kazan', 420029

  • FSBI National Medical Oncology Research Center n.a. N.N. Blokhina

    Moscow, 115478

  • FSBI-FRCC of Special Types Med. Care & Technologies FMBA of Russia

    Moscow, 115682

  • Leningrad Regional Oncology Center

    Saint Petersburg, 191014

  • SPb SBHI City Clinical Oncological Dispensary

    Saint Petersburg, 198255

  • Mordovia Republican Oncological Dispensary

    Saransk, 430032

  • Tomsk National Research Medical Center of Russian Academy of Sciences

    Tomsk, 624028

  • Republican Clinical Oncology Dispensary of Republic of Bashkortostan

    Ufa, 450054

Other trials in Russia

United Kingdom9 sites

  • Royal Sussex County Hospital

    Brighton, BN2 5BE

  • Addenbrookes Hospital

    Cambridge, CB2 0QQ

  • Barts Health NHS Trust - St Bartholomew s Hospital

    London, EC1A 7BE

  • Guy s & St Thomas NHS Foundation Trust

    London, SE1 9RT

  • The Royal Marsden Foundation Trust

    London, SM2 5PT

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Imperial College Healthcare NHS Trust

    London, W12 0HS

  • University College Hospital

    London, WC1E 6AG

  • University Hospital Southampton NHS Foundation Trust

    Southampton, SO16 6YD

Other trials in United Kingdom

Brazil8 sites

  • Faculdade de Medicina da Universidade Federal de Minas Gerais

    Belo Horizonte, 30130-100

  • Hospital Araujo Jorge

    Goiânia, Goiás, 74175-120

  • Fundacao Dr Amaral Carvalho

    Jaú, São Paulo, 17210-080

  • Hospital de Clinicas de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Instituto Nacional do Cancer II

    Rio de Janeiro, Rio de Janeiro, 20220-410

  • Instituto do Cancer de Sao Paulo - ICESP

    São Paulo, São Paulo, 01246-000

  • Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda

    São Paulo, São Paulo, 01317-000

Other trials in Brazil

Poland8 sites

  • Beskidzkie Centrum Onkologii im. Jana Pawla II

    Bielsko-Biala, 43-300

  • Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o.

    Gdynia, 81-159

  • Centrum Onkologii Instytut im. Marii Sklodowskiej Curie

    Gliwice, 44-101

  • Centrum Onkologii Instytut im. Marii Sklodowskiej Curie

    Krakow, Lesser Poland Voivodeship, 31-115

  • Instytut Centrum Zdrowia Matki Polki

    Lodz, 93-338

  • Pomorski Uniwersytet Medyczny w Szczecinie

    Szczecin, 70-111

  • Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie

    Warsaw, Masovian Voivodeship, 02-781

  • Szpital Kliniczny im Ks Anny Mazowieckiej

    Warsaw, 00-315

Other trials in Poland

Argentina7 sites

  • Centro de Oncologia e Investigacion Buenos Aires COIBA

    Berazategui, Buenos Aires, B1884BBF

  • Instituto de Investigaciones Metabolicas

    Buenos Aires, C1012AAR

  • Hospital Aleman

    Buenos Aires, C1118AAT

  • Instituto de Oncologia Angel H. Roffo

    Buenos Aires, C1417DTB

  • Instituto Medico Especializado Alexander Fleming

    Buenos Aires, C1426ANZ

  • Centro Oncologico Riojano Integral

    La Rioja, F5300COE

  • Hospital Privado de la Comunidad

    Mar del Plata, Buenos Aires, B7602CBM

Other trials in Argentina

Colombia7 sites

  • Biomelab S A S

    Barranquilla, 08002

  • Clinica del Country

    Bogota, Cundinamarca, 110221

  • Clinica Colsanitas S.A. - Sede Clinica Universitaria Colombia

    Bogotá, 111321

  • Fundacion Valle del Lili

    Cali, Valle del Cauca Department, 760032

  • Rodrigo Botero SAS

    Medellín, 50015

  • Fundacion Colombiana de Cancerologia Clinica Vida

    Medellín, 50032

  • Oncomedica S.A.

    Montería, 230002

Other trials in Colombia

Italy7 sites

  • Azienda Ospedaliera per l Emergenza Cannizzaro

    Catania, 95126

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola, 47014

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • Ospedale San Raffaele

    Milan, 20132

  • Istituto Europeo di Oncologia

    Milan, 20141

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale

    Naples, 80131

  • Policlinico Universitario Agostino Gemelli

    Roma, 168

Other trials in Italy

Spain7 sites

  • Hospital General Universitari Vall d Hebron

    Barcelona, 8035

  • Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals

    L'Hospitalet de Llobregat, Barcelona, 8908

  • Hospital Universitario Gregorio Maranon

    Madrid, 28007

  • Clinica Universitaria Navarra - Madrid

    Madrid, 28027

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario y Politecnico La Fe de Valencia

    Valencia, 46026

Other trials in Spain

Turkey (Türkiye)7 sites

  • Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi

    Adana, 01250

  • Hacettepe University Medical Faculty

    Ankara, 06000

  • Baskent Universitesi Ankara Hastanesi

    Ankara, 06490

  • Acibadem Bursa Hastanesi

    Bursa, 16110

  • Acibadem Universitesi Atakent Hastanesi

    Istanbul, 34303

  • Florence Nightingale Gayrettepe Hastanesi

    Istanbul, 34349

  • Ege Universitesi Tip Fakultesi

    Izmir, 35040

Other trials in Turkey (Türkiye)

Germany6 sites

  • EISAI Trial Site 4

    Berlin

  • EISAI Trial Site 2

    Dresden

  • EISAI Trial Site 1

    Erlangen

  • EISAI Trial Site 6

    Hamburg

  • EISAI Trial Site 3

    Rostock

  • EISAI Trial Site 5

    Tübingen

Other trials in Germany

Israel6 sites

  • Soroka Medical Center

    Beersheba, 84101

  • Rambam Medical Center

    Haifa, 3525408

  • Edith Wolfson Medical Center

    Holon, 5822012

  • Hadassah Medical Center. Ein Kerem

    Jerusalem, 9112001

  • Rabin Medical Center

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center

    Ramat Gan, 5262000

Other trials in Israel

Taiwan6 sites

  • Kaohsiung Veterans General Hospital

    Kaohsiung City, 813

  • Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F.

    Kaohsiung City, 833

  • Taichung Veterans General Hospital

    Taichung, 40705

  • Taipei Veterans General Hospital

    Taipei, Beitou, 11217

  • National Taiwan University Hospital

    Taipei, 10002

  • Chang Gung Medical Foundation. Linkou Branch

    Taoyuan, 33305

Other trials in Taiwan

Mexico5 sites

  • Investigacion Onco Farmaceutica S de RL de CV

    La Paz, Estado de Baja California, 23040

  • Grupo Medico Camino SC

    Mexico City, 3310

  • Alivia Clinica de Alta Especialidad S.A. de C.V.

    Monterrey, Nuevo León, 64060

  • Centro Hemato Oncologico Privado

    Toluca, 50080

  • Faicic S de RL de CV

    Veracruz, 91900

Other trials in Mexico

Australia4 sites

  • Royal Brisbane and Women s Hospital

    Herston, Queensland, 4029

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • St John of God

    Subiaco, Western Australia, 6008

  • Royal North Shore Hospital

    Sydney, New South Wales, 2065

Other trials in Australia

South Korea4 sites

  • National Cancer Center

    Goyang-si, Gyeonggi-do, 10408

  • Seoul National University Hospital

    Seoul, 3080

  • Asan Medical Center

    Seoul, 5505

  • Samsung Medical Center

    Seoul, 6351

Other trials in South Korea

Ireland1 site

  • Mater Misericordiae University Hospital

    Dublin, D07 R2WY

Other trials in Ireland

New Zealand1 site

  • Auckland City Hospital

    Auckland, 1023

Other trials in New Zealand

About this study

Official title: 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.

Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2), vascular endothelial growth factor (VEGF) receptors, lenvatinib, pembrolizumab, doxorubicin, paclitaxel, phase 3 endometrial cancer
Medical subject headings
Endometrial Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called KEYTRUDA®, MK-3475

    200 mg administered by IV infusion on Day 1 of each 21-day cycle.

  • LenvatinibDrug

    Also called LENVIMA®

    20 mg administered orally (PO) QD during each 21-day cycle.

  • PaclitaxelDrug

    Also called TAXOL®

    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.

  • DoxorubicinDrug

    Also called ADRIAMYCIN®

    60 mg/m^2 administered by IV on Day 1 of each 21-day cycle.

Study groups in NCT03517449
Study groupRoleWhat they receive
Lenvatinib 20 mg + Pembrolizumab 200 mgExperimentalParticipants 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.
Receives: Drug: Pembrolizumab; Drug: Lenvatinib
Treatment of Physician's ChoiceActive comparatorParticipants 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.
Receives: Drug: Paclitaxel; Drug: Doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to approximately 27 months

  2. 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.

    Measured: Up to approximately 27 months

  3. 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.

    Measured: Up to approximately 43 months

  4. 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.

    Measured: Up to approximately 43 months

Secondary outcomes (13)

  1. 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.

    Measured: Up to approximately 80 months

  2. 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.

    Measured: Up to approximately 80 months

  3. 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.

    Measured: Baseline, Week 12

  4. 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.

    Measured: Baseline, Week 12

  5. 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.

    Measured: Up to approximately 77 months

  6. 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.

    Measured: Up to approximately 77 months

  7. 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.

    Measured: Up to approximately 77 months

  8. 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.

    Measured: Up to approximately 77 months

  9. 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.

    Measured: Up to approximately 77 months

  10. 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.

    Measured: 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)

  11. 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.

    Measured: 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)

  12. 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.

    Measured: 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)

  13. 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.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2018
  2. Study start11 Jun 2018
  3. Primary completion1 Mar 2022
  4. Study completion26 Feb 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
827 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03517449
Sponsor's protocol ID
E7080-G000-309
Other IDs
2017-004387-35, MK3475-775, 2017
Status last verified
Feb 2026
First submitted
25 Apr 2018
Last updated
19 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Marth C, Lorusso D, Bidzinski M, Scollo P, Vardar MA, Oaknin A, Kaen DL, Nogueira-Rodrigues A, Miller DS, Hasegawa K, MacKay H, Moore RG, Santin AD, Yunokawa M, Romero I, Pignata S, Baron-Hay S, Kim YM, Amit A, Ghamande S, Danska-Bidzinska A, Tarnawski R, Wang PH, Yu Z, Slomovitz BM, Okpara CE, McKenzie J, Meng R, Orlowski R, Makker V. Lenvatinib plus pembrolizumab in participants with advanced or recurrent endometrial cancer: Study 309/KEYNOTE-775 and ENGOT-en9/LEAP-001 post-(neo)adjuvant therapy outcomes. Int J Gynecol Cancer. 2026 Jul;36(7):104693. doi: 10.1016/j.ijgc.2026.104693. Epub 2026 Apr 12.

    PubMed 42167105

  • 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.

    PubMed 38302725

  • 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.

    PubMed 37523661

  • 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.

    PubMed 37086595

  • 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.

    PubMed 37058687

  • 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.

    PubMed 35045221

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Lenvatinib and Paclitaxel in people with Endometrial Neoplasms, run by Eisai Inc. at 169 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 169 sites in United States, Japan, France, Canada, Russia and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to approximately 27 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03517449, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.

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