Metastatic Esophageal Squamous Cell CarcinomaPhase 3NCT04949256
Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014).
A Phase 3 study testing Pembrolizumab, Lenvatinib and Cisplatin in people with Metastatic Esophageal Squamous Cell Carcinoma, run by Merck Sharp & Dohme LLC at 198 sites in 25 countries.
Trial summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Esophageal Squamous Cell Carcinoma
- What is being tested?
- Pembrolizumab, Lenvatinib and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 863 participants
- Where
- 198 sitesin 25 countries
- Study dates
- 28 Jul 2021to 20 May 2026
- Phase
- Phase 3
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus
- Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception is needed
- Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this period
- Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization
- Has adequate organ function
Who cannot join
- Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer
- Has locally advanced esophageal carcinoma
- Has metastatic adenocarcinoma of the esophagus
- Has direct invasion into adjacent organs such as the aorta or trachea
- Has radiographic evidence of encasement of a major blood vessel, or of intratumoral cavitation
- Has perforation risks or significant gastrointestinal (GI) bleeding
Show all 23Show fewer
- Has had clinically significant hemoptysis within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention
- Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
- Has GI obstruction, poor oral intake, difficulty in taking oral medication, or existing esophageal stent
- Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to first dose of study interventions
- Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis
- Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention, or has a history of organ transplant, including allogeneic stem cell transplant
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
- Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- Has poorly controlled diarrhea
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
- Has peripheral neuropathy ≥Grade 2
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B or know active Hepatitis C virus infection
- Has a weight loss of >20% within the last 3 months
Trial locations and contacts
198 sites in 25 countries.
198 sites in 25 countries
China29 sites
Anyang Cancer Hospital ( Site 8006)
Anyang, Henan, 455000
Beijing Cancer Hospital ( Site 8001)
Beijing, Beijing Municipality, 100142
Jilin Cancer Hospital ( Site 8016)
Changchun, Jilin, 130012
The Third Xiangya Hospital of Central South University ( Site 8046)
Changsha, Hainan, 410013
Affiliated Hospital of Chengde Medical Univeristy ( Site 8053)
Chengde, Hebei, 067055
West China Hospital of Sichuan University ( Site 8048)
Chengdu, Sichuan, 610041
Fujian Provincial Cancer Hospital ( Site 8029)
Fuzhou, Fujian, 350014
The First Affiliated Hospital.Sun Yat-sen University ( Site 8047)
Guangzhou, Guangdong, 510080
Southern Medical University Nanfang Hospital ( Site 8031)
Guangzhou, Guangdong, 510515
The First Affiliated Hospital of Hainan Medical University ( Site 8042)
Haikou, Hainan, 570102
Sir Run Run Shaw Hospital ( Site 8021)
Hangzhou, Zhejiang, 310016
Harbin Medical University Cancer Hospital ( Site 8009)
Harbin, Heilongjiang
Anhui Provincial Cancer Hospital ( Site 8058)
Hefei, Anhui, 230031
The Second Affiliated Hospital of Anhui Medical University ( Site 8026)
Hefei, Anhui, 230031
Jinan Central Hospital ( Site 8052)
Jinan, Shandong, 250013
Shandong Cancer Hospital ( Site 8060)
Jinan, Shandong, 250117
Affiliated Hospital of Jining Medical University ( Site 8017)
Jining, Shandong, 272000
Linyi Cancer Hospital- Medical Oncology Department ( Site 8051)
Linyi, Shandong, 276000
The First Affiliated Hospital of Henan University of Science &Technology-Tumor ( Site 8036)
Luoyang, Henan, 471003
Shanxi Provincial Cancer Hospital ( Site 8019)
Taiyuan, Shanxi, 030000
Tianjin Medical University Cancer Institute & Hospital ( Site 8035)
Tianjin, Tianjin Municipality, 300060
The Affiliated Cancer Hospital of Xinjiang Medical University. ( Site 8041)
Ürümqi, Xinjiang, 830000
Tongji Medical College Huazhong Uinversity Of Science and Technology ( Site 8025)
Wuhan, Hubei, 430030
Hubei Cancer Hospital ( Site 8014)
Wuhan, Hubei, 430079
Affiliated hospital of Jiangnan university ( Site 8049)
Wuxi, Jiangsu, 214122
Zhongshan Hospital Affiliated to Xiamen University ( Site 8055)
Xiamen, Fujian, 361004
The First Affiliated Hospital of Xiamen University ( Site 8003)
Xiamen City, Fujian Province, Fujian, 361003
The First Affiliated Hospital of Xinxiang Medical University ( Site 8018)
Xinxiang, Henan, 453100
The Affiliated Hospital of Xuzhou Medical University ( Site 8015)
Xuzhou, Jiangsu, 221000
Japan27 sites
Hyogo Cancer Center ( Site 9014)
Akashi, Hyōgo, 673-8558
Tokyo Metropolitan Komagome Hospital ( Site 9028)
Bunkyo Ku, Tokyo, 113-8677
Chiba Cancer Center ( Site 9023)
Chiba, Chiba, 260-8717
National Hospital Organization Kyushu Cancer Center ( Site 9010)
Fukuoka, 811-1395
Ibaraki Prefectural Central Hospital ( Site 9007)
Kasama, Ibaraki, 309-1793
National Cancer Center Hospital East ( Site 9002)
Kashiwa, Chiba, 277-8577
Kagawa University Hospital ( Site 9015)
Kita-gun, Kagawa-ken, 761-0793
Saitama Prefectural Cancer Center ( Site 9003)
Kitaadachi-gun, Saitama, 362-0806
University Hospital,Kyoto Prefectural University of Medicine ( Site 9027)
Kyoto, 602-8566
Kyoto University Hospital ( Site 9011)
Kyoto
National Hospital Organization Shikoku Cancer Center ( Site 9019)
Matsuyama, Ehime, 791-0280
Toranomon Hospital ( Site 9026)
Minato-ku, Tokyo, 105-8470
Aichi Cancer Center Hospital ( Site 9006)
Nagoya, Aichi-ken, 464-8681
Shizuoka Cancer Center ( Site 9016)
Nakatogari, Shizuoka, 411-8777
Niigata Cancer Center Hospital ( Site 9022)
Niigata, Niigata, 951-8566
Okayama University Hospital ( Site 9024)
Okayama, 700-8558
Osaka International Cancer Institute ( Site 9009)
Osaka, 541-8567
Osaka General Medical Center ( Site 9018)
Osaka, 558-8558
Kindai University Hospital ( Site 9017)
Sayama, Osaka, 589-8511
Tohoku University Hospital ( Site 9013)
Sendai, Miyagi, 980-8574
Showa University Hospital ( Site 9025)
Shinagawa, Tokyo, 142-8666
Osaka University Hospital ( Site 9021)
Suita, Osaka, 565-0871
Osaka Medical and Pharmaceutical University Hospital ( Site 9008)
Takatsuki, Osaka, 569-8686
National Cancer Center Hospital ( Site 9001)
Tokyo, 104-0045
The Cancer Institute Hospital of JFCR ( Site 9005)
Tokyo, 135-8550
Keio University Hospital ( Site 9020)
Tokyo, 160-8582
Kanagawa Cancer Center ( Site 9004)
Yokohama, Kanagawa, 241-8515
United States15 sites
Johns Hopkins Bayview Medical Center ( Site 0152)
Baltimore, Maryland, 21224
St. Luke's University Health Network ( Site 0185)
Bethlehem, Pennsylvania, 18015
Medical University of South Carolina-Hollings Cancer Center ( Site 0177)
Charleston, South Carolina, 29425
City of Hope ( Site 0102)
Duarte, California, 91010
Hematology-Oncology Associates of CNY ( Site 0173)
East Syracuse, New York, 13057
James Graham Brown Cancer Center ( Site 0117)
Louisville, Kentucky, 40202
Norton Cancer Institute ( Site 0116)
Louisville, Kentucky, 40217
Memorial Sloan Kettering Cancer Center ( Site 0132)
New York, New York, 10065
Weill Cornell Medical College ( Site 0133)
New York, New York, 10065
Capital Health Medical Center - Hopewell ( Site 0189)
Pennington, New Jersey, 08534
AHN Allegheny General Hospital ( Site 0164)
Pittsburgh, Pennsylvania, 15212
VCU Health Adult Outpatient Pavillion ( Site 0160)
Richmond, Virginia, 23219
Seattle Cancer Care Alliance ( Site 0145)
Seattle, Washington, 98109
MedStar Washington Hospital Center ( Site 0186)
Washington D.C., District of Columbia, 20010
UMASS Memorial Medical Center ( Site 0120)
Worcester, Massachusetts, 01655
France13 sites
CHU Besançon ( Site 1015)
Besançon, Franche-Comte, 25000
C.H. regional Unv. de Brest - Hopital La Cavale Blanche - Institut de Cancerologie et d Imagerie ( S
Brest, Finistere, 29200
Centre François Baclesse ( Site 1009)
Caen, Calvados, 14076
Hopital Henri Mondor ( Site 1007)
Créteil, Val-de-Marne, 94010
Centre Georges Francois Leclerc ( Site 1008)
Dijon, Cote-d Or, 21000
Hôpital Claude Huriez ( Site 1030)
Lille, Nord, 59000
Institut du Cancer de Montpellier ( Site 1002)
Montpellier, Herault, 34298
Hopital Saint Louis ( Site 1029)
Paris, 75010
CHU Bordeaux Haut-Leveque ( Site 1012)
Pessac, Gironde, 33604
Institut De Cancerologie De L Ouest ( Site 1003)
Saint-Herblain, Loire-Atlantique, 44805
Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1014)
Strasbourg, Alsace, 67200
CHRU de Tours - Hopital Bretonneau ( Site 1018)
Tours, Indre-et-Loire, 37044
Institut De Cancerologie De Lorraine ( Site 1010)
Vandœuvre-lès-Nancy, Ain, 54519
Italy12 sites
Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1314)
Catanzaro, 88100
Azienda Ospedaliero Universitaria Careggi ( Site 1301)
Florence, 50134
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 1313)
Meldola, Emilia-Romagna, 47014
IRCCS Ospedale San Raffaele di Milano ( Site 1304)
Milan, 20132
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1306)
Milan, 20133
A.O. Universitaria di Modena ( Site 1307)
Modena, 41124
A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1305)
Naples, 80131
Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 1311)
Padova, Veneto, 35128
Azienda Ospedaliera Universitaria Pisana ( Site 1312)
Pisa, Tuscany, 56126
Universita Cattolica del Sacro Cuore - Policlinico Gemelli ( Site 1310)
Roma, 00168
Humanitas Research Hospital ( Site 1309)
Rozzano, Lombardy, 20089
A.O.U. Santa Maria della Misericordia di Udine ( Site 1302)
Udine, Friuli Venezia Giulia, 33100
Argentina11 sites
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0203)
Berazategui, Buenos Aires, B1884BBF
Fundacion Favaloro ( Site 0201)
Buenos Aires, C1093AAS
Fundación Respirar ( Site 0216)
Buenos Aires, C1426ABP
IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)
CABA, Buenos Aires, C1012AAR
Hospital Italiano de Córdoba ( Site 0218)
Córdoba, X5004BAL
Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0221)
La Rioja, F5300COE
Instituto de Investigaciones Clinicas Mar del Plata ( Site 0205)
Mar del Plata, Buenos Aires, B7600FZO
Fundacion Estudios Clinicos-Oncology ( Site 0215)
Rosario, Santa Fe Province, S2000DEJ
Sanatorio Parque ( Site 0206)
Rosario, Santa Fe Province, S2000DSV
Hospital Provincial del Centenario ( Site 0217)
Rosario, Santa Fe Province, S2002KDS
Instituto San Marcos ( Site 0213)
San Juan, J5400EBB
Ukraine11 sites
Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (
Antonivka Village, Kherson Oblast, 73000
Chernihiv Medical Center of Modern Oncology ( Site 1811)
Chernihiv, Chernihiv Oblast, 14029
Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center" ( Site 1819)
Chernivtsi, Chernivetska Oblast, 58013
Kharkiv Regional Clinical Oncology Center ( Site 1812)
Kharkiv, Kharkiv Oblast, 61000
Institute of General and Emergency Surgery n.a Zaitsev NAMS of Ukraine ( Site 1813)
Kharkiv, Kharkiv Oblast, 61103
MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council ( Site 1804)
Kryviy Rih, Dnipropetrovsk Oblast, 50048
SNPE National Cancer Institute ( Site 1806)
Kyiv, Kyivska Oblast, 03022
Shalimov Institute of Surgery and Transplantation ( Site 1818)
Kyiv, 03126
Volyn Regional Oncological Dispensary ( Site 1816)
Lutsk, Volyn Oblast, 43018
Rivne Regional Clinical Hospital ( Site 1817)
Rivne, Rivne Oblast, 33007
Podillya Regional Center of Oncology ( Site 1809)
Vinnytsia, Vinnytsia Oblast, 21029
United Kingdom9 sites
Cambridge University Hospitals NHSFT ( Site 1908)
Cambridge, Cambridgeshire, CB2 2QQ
Ninewells Hospital and Medical School ( Site 1907)
Dundee, Dundee City, DD2 1SG
Western General Hospital ( Site 1912)
Edinburgh, Midlothian, EH4 2XU
St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1915)
London, London, City of, EC1A 7BE
University College London Hospitals NHS Foundation Trust ( Site 1901)
London, London, City of, NW1 2BU
Royal Marsden NHS Foundation Trust ( Site 1905)
London, London, City of, SW3 6JJ
The Christie NHS Foundation Trust ( Site 1909)
Manchester, M20 4BX
Nottingham University Hospital NHS Trust ( Site 1910)
Nottingham, England, NG5 1PF
Royal Marsden NHS Trust. ( Site 1906)
Sutton, London, City of, SM2 5PT
Turkey (Türkiye)8 sites
Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 1714)
Adana, 01140
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1701)
Ankara, 06230
Memorial Ankara Hastanesi ( Site 1702)
Ankara, 06520
Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 1715)
Ankara, 06800
Atatürk Üniversitesi-onkoloji ( Site 1712)
Erzurum, 25070
Acibadem Universitesi Atakent Hastanesi-Medical Oncology ( Site 1716)
Istanbul, 34303
Istanbul Okmeydanı Egitim ve Arastirma Hastanesi ( Site 1711)
Istanbul, 34384
Medeniyet Universitesi Tip Fakultesi ( Site 1703)
Istanbul, 34732
Russia7 sites
Republican Clinical Oncology Dispensary of Tatarstan MoH named after professor M.Z. Sigal ( Site 150
Kazan', Tatarstan, Respublika, 420029
FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1510)
Moscow, Moscow, 115478
Academician I.P. Pavlov First St. Petersburg State Medical University ( Site 1519)
Saint Petersburg, Sankt-Peterburg, 197022
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1503)
Saint Petersburg, Sankt-Peterburg, 197758
GBUZ LOKB ( Site 1502)
Saint-Petersburg, Leningradskaya Oblast', 194291
SAIH of Tyumen reg "Multifield clinical medical center "Medical city" ( Site 1520)
Tyumen, Tyumen Oblast, 625041
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)
Ufa, Baskortostan, Respublika, 450054
Chile6 sites
Fundacion Arturo Lopez Perez FALP ( Site 0403)
Santiago, Region M. de Santiago, 7500836
Oncovida ( Site 0413)
Santiago, Region M. de Santiago, 7510032
Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)
Santiago, Region M. de Santiago, 7550000
Bradford Hill Centro de Investigaciones Clinicas ( Site 0404)
Santiago, Region M. de Santiago, 8420383
James Lind Centro de Investigacion del Cancer ( Site 0412)
Temuco, Araucania, 4800827
Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0401)
Temuco, Araucania, 4810218
Romania6 sites
MEMORIAL HEALTHCARE INTERNATIONAL S.R.L. ( Site 2201)
Bucharest, Bucharest, 013812
Cardiomed SRL Cluj-Napoca-Medical Oncology ( Site 2207)
Cluj-Napoca, Cluj, 400015
SC Radiotherapy Center Cluj SRL ( Site 2202)
Comuna Floresti, Cluj, 407280
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2204)
Craiova, Dolj, 200542
Ovidius Clinical Hospital OCH-Oncology and Hematology ( Site 2203)
Ovidiu, Constanța County, 905900
Policlinica Oncomed SRL ( Site 2206)
Timișoara, Timiș County, 300239
Spain6 sites
Hospital General Universitari Vall d Hebron ( Site 1607)
Barcelona, 08035
Hospital General Universitario Gregorio Maranon ( Site 1604)
Madrid, 28007
Complexo Hospitalario Universitario de Ourense-MEDICAL ONCOLOGY ( Site 1609)
Ourense, Orense, 32005
Hospital Universitario General de Asturias ( Site 1601)
Oviedo, Principality of Asturias, 33011
Hospital Universitario Marques de Valdecilla ( Site 1602)
Santander, Cantabria, 39008
Hospital Virgen del Rocio ( Site 1606)
Seville, 41013
Taiwan6 sites
Chang Gung Med Foundation. Kaohsiung Branch ( Site 6005)
Kaohsiung City, 833
China Medical University Hospital ( Site 6003)
Taichung, 40447
Chi Mei Hospital - Liouying Branch-Clinical Trial Center ( Site 6007)
Tainan, Tainan, 73657
National Cheng Kung University Hospital ( Site 6004)
Tainan, 704
National Taiwan University Hospital ( Site 6001)
Taipei, 10002
Taipei Veterans General Hospital ( Site 6006)
Taipei, 11217
South Korea5 sites
Seoul National University Bundang Hospital ( Site 5006)
Seongnam-si, Kyonggi-do, 13605
Severance Hospital ( Site 5003)
Seoul, 03722
Samsung Medical Center ( Site 5005)
Seoul, 06351
Korea University Guro Hospital ( Site 5001)
Seoul, 08308
Asan Medical Center ( Site 5002)
Songpagu, Seoul, 05505
Costa Rica4 sites
ICIMED-Oncology Research Unit ( Site 0903)
San José, Provincia de San José, 10108
PROCLINICAL Pharma ( Site 0904)
San José, Provincia de San José, 11303
CIMCA Centro de Investigacion y Manejo del Cancer ( Site 0902)
San José, 10103
Onco Tech S A ( Site 0901)
San José, 10103
Guatemala4 sites
Centro Regional de Sub Especialidades Medicas SA ( Site 0604)
Guatemala, Departamento de Quetzaltenango, 09001
MEDI-K ( Site 0601)
Guatemala City, 01009
Oncomedica ( Site 0602)
Guatemala City, 01010
Soluciones Gastrointestinales S.A. ( Site 0607)
Guatemala City, 01010
Hungary4 sites
Orszagos Onkologiai Intezet ( Site 1207)
Budapest, 1122
Petz Aladar Egyetemi Oktato Korhaz ( Site 1210)
Győr, Győr-Moson-Sopron, 9024
Pecsi Tudomanyegyetem AOK ( Site 1204)
Pécs, Baranya, 7624
Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1203)
Szolnok, Jász-Nagykun-Szolnok, 5000
Canada3 sites
Hotel-Dieu de Levis ( Site 0013)
Lévis, Quebec, G6V 3Z1
Princess Margaret Cancer Centre ( Site 0004)
Toronto, Ontario, M5G 2M9
CancerCare Manitoba ( Site 0001)
Winnipeg, Manitoba, R3E 0V9
Malaysia3 sites
Hospital Kuala Lumpur ( Site 9104)
Kuala Lumpur, 50586
Sarawak General Hospital-Radiotherapy Unit ( Site 9100)
Kuching, Sarawak, 93586
University Malaya Medical Centre ( Site 9101)
Lembah Pantai, Kuala Lumpur, 59100
Denmark2 sites
Rigshospitalet ( Site 2102)
Copenhagen, Capital Region, 2100
Odense University Hospital ( Site 2101)
Odense, Region Syddanmark, 5000
Hong Kong2 sites
Queen Mary Hospital ( Site 4001)
Hong Kong
Queen Elizabeth Hospital. ( Site 4004)
Kowloon
South Africa2 sites
The Oncology Centre ( Site 9505)
Durban, KwaZulu-Natal, 4091
Wits Clinical Research ( Site 9502)
Johannesburg, Gauteng, 2193
Thailand2 sites
Faculty of Medicine Siriraj Hospital ( Site 7002)
Bangkok, Bangkok, 10700
Songklanagarind hospital ( Site 7001)
Hat Yai, Changwat Songkhla, 90110
Singapore1 site
National Cancer Centre Singapore ( Site 9201)
Singapore, Central Singapore, 168583
About this study
Official title: A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma.
The primary hypotheses are that pembrolizumab plus lenvatinib plus chemotherapy is superior to pembrolizumab plus chemotherapy with respect to overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
As of Amendment 09, Study MK-7902-014 will begin close out activities. Any participant who discontinues study intervention for any reason will be discontinued from the study without further follow-up. Second Course and treatment beyond disease progression will no longer be offered. No safety concerns contributed to the termination of this study.
Read the detailed description
There will be 2 parts to the study: the cisplatin and 5-fluorouracil (5-FU) (FP) and paclitaxel and cisplatin (TP) Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (FP and TP Safety Run-in), participants will be treated with pembrolizumab plus lenvatinib plus FP or TP. Dose-limiting toxicities, safety, and tolerability will be assessed.
In Part 2 (Main Study), participants (not including those participating in Part 1) will be treated with pembrolizumab plus lenvatinib plus chemotherapy or pembrolizumab plus chemotherapy. Efficacy, safety, and tolerability will be assessed.
The protocol-specified analysis of the primary outcome measures was completed with a data cut-off of 08-May-2025 (Primary Completion Date) and served as the final analysis of the primary outcome measures. At the time of the protocol-specified analysis, 368 participants were ongoing in the study and will be included in the End of Trial analysis.
- Being tested
- Pembrolizumab, Lenvatinib, Cisplatin, 5-FU, Oxaliplatin
- Keywords
- programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, 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.
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
400 mg once every 6-week-cycle, via IV infusion.
LenvatinibDrug
Also called MK-7902, E7080, LENVIMA®
8 mg QD (Induction) or 20 mg QD (Consolidation) via oral capsule.
CisplatinDrug
Also called PLATINOL®
80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 75 mg/m^2 Q3W via infusion, as part of investigator's choice TP chemotherapy.
5-FUDrug
Also called ADRUCIL®
4000 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 400 mg/m^2 Q2W via bolus IV infusion followed by 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.
OxaliplatinDrug
Also called ELOXATIN®
85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.
LeucovorinDrug
Also called calcium folinate, folinic acid, WELLCOVORIN®
400 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
LevoleucovorinDrug
Also called calcium levofolinate, levofolinic acid, FUSILEV®
200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
PaclitaxelDrug
Also called TAXOL®, ONXAL®
175 mg/m^2 Q3W via IV infusion, as part of investigator's choice TP chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Pembrolizumab + Lenvatinib + Chemotherapy | Experimental | In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 400 mg/m^2 followed by 2400 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks). Receives: Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Cisplatin; Drug: 5-FU; Drug: Paclitaxel |
| Part 2: Pembrolizumab + Lenvatinib + Chemotherapy | Experimental | In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks). Receives: Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Cisplatin; Drug: 5-FU; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Levoleucovorin; Drug: Paclitaxel |
| Part 2: Pembrolizumab + Chemotherapy | Active comparator | Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]). Receives: Biological: Pembrolizumab; Drug: 5-FU; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Levoleucovorin; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT is defined as a specific adverse event graded for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Hematologic DLTs are defined as Grade 4 neutropenia lasting for ≥7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT include any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting >3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, ≥Grade 3 gastrointestinal perforation, ≥Grade 3 wound dehiscence requiring medical or surgical intervention, any grade thromboembolic event or any Grade 3 nonhematologic laboratory value requiring medical intervention or hospitalization. The number of participants in Part 1 with DLTs are presented.
Measured: Up to 21 days
Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 with AEs will be presented.
Measured: Up to 43 months
Part 1 (FP and TP Safety Run-in): Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
Measured: Up to 22 months
Part 2 (Main Study): Overall Survival (OS) in All Participants
OS is defined as the time from randomization to death due to any cause. OS in Part 2 for all randomized participants are presented based on the Kaplan-Meier method for censored data.
Measured: Up to 42 months
Secondary outcomes (9)
Part 2 (Main Study): Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in All Participants
PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS in Part 2 for all randomized participants are presented based on the Kaplan-Meier method for censored data.
Measured: Up to 42 months
Part 2 (Main Study): Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in All Participants
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 adjusted to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR. ORR in Part 2 for all randomized participants are presented.
Measured: Up to 42 months
Part 2 (Main Study): Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in All Participants
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 by BICR, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR in Part 2 for all randomized participants are presented based on the Kaplan-Meier method for censored data.
Measured: Up to 42 months
Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10
OS is defined as the time from randomization to death due to any cause. OS in Part 2 for randomized participants with PD-L1 CPS ≥10 are presented based on the Kaplan-Meier method for censored data.
Measured: Up to 42 months
Part 2 (Main Study): PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS in Part 2 for randomized participants with PD-L1 CPS ≥10 are presented based on the Kaplan-Meier method for censored data.
Measured: Up to 42 months
Part 2 (Main Study): ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
ORR is defined as the percentage of participants with CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 adjusted to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR. ORR in Part 2 for randomized participants with PD-L1 CPS ≥10 are presented.
Measured: Up to 42 months
Part 2 (Main Study): DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 by BICR, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR in Part 2 for randomized participants with PD-L1 CPS ≥10 are presented based on the Kaplan-Meier method for censored data.
Measured: Up to 42 months
Part 2 (Main Study): Number of Participants With AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 2 with AEs are presented.
Measured: Up to 43 months
Part 2 (Main Study): Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 2 who discontinue study treatment due to an AE are presented.
Measured: Up to 22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2021
- Study start28 Jul 2021
- Primary completion8 May 2025
- Study completion20 May 2026
Why it stopped: Trial was rendered as cancelled work ongoing in the book of business.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Esophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 863 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04949256
- Sponsor's protocol ID
- 7902-014
- Other IDs
- MK-7902-014, LEAP-014, E7080-G000-320, U1111-1280-1020, 2022-501342-29-00, 2020-001911-26
- Status last verified
- Aug 2026
- First submitted
- 29 Jun 2021
- Last updated
- 21 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Sun JM, Adenis A, C Enzinger P, Shah MA, Kato K, Bennouna J, Doi T, Hawk NN, Yu L, Shah S, Bhagia P, Shen L. LEAP-014: first-line lenvatinib + pembrolizumab + chemotherapy in advanced/metastatic esophageal squamous cell carcinoma. Future Oncol. 2024;20(35):2709-2721. doi: 10.2217/fon-2022-1148. Epub 2024 May 2.
PubMed 38695479