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)

NCT04949256 | Active Not Recruiting Phase 3 DMC FDA Drug

• 7 other identifiers: 7902-014MK-7902-014LEAP-014E7080-G000-320U1111-1280-10202022-501342-29-002020-001911-26
• Study Type: interventional
• Target: 864
• Locations: 25 countries
• Sites: 198

Brief 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. 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.

Conditions

Metastatic Esophageal Squamous Cell Carcinoma

Keywords

programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1)

Outcome Measures

Primary Outcomes (4)

• Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)

  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 will be presented.

  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.

  Up to ~53 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.

  Up to ~53 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 will be presented.

  Up to ~48 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

  Up to ~42 months

• Part 2 (Main Study): Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR in all Participants

  Up to ~42 months

• Part 2 (Main Study): Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR in all Participants

  Up to ~42 months

• Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10

  Up to ~48 months

• Part 2 (Main Study): PFS per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10

  Up to ~42 months

Study Arms (3)

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).

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).

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 \[approximately 2 years\]).

Biological: Pembrolizumab; Drug: 5-FU; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Levoleucovorin; Drug: Paclitaxel

Interventions

Pembrolizumab BIOLOGICAL

400 mg once every 6-week-cycle, via IV infusion.

Also known as: MK-3475, KEYTRUDA®

Part 1: Pembrolizumab + Lenvatinib + Chemotherapy; Part 2: Pembrolizumab + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Lenvatinib DRUG

8 mg QD (Induction) or 20 mg QD (Consolidation) via oral capsule.

Also known as: MK-7902, E7080, LENVIMA®

Part 1: Pembrolizumab + Lenvatinib + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Cisplatin DRUG

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.

Also known as: PLATINOL®

Part 1: Pembrolizumab + Lenvatinib + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

5-FU DRUG

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.

Also known as: ADRUCIL®

Part 1: Pembrolizumab + Lenvatinib + Chemotherapy; Part 2: Pembrolizumab + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Oxaliplatin DRUG

85 mg/m\^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.

Also known as: ELOXATIN®

Part 2: Pembrolizumab + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Leucovorin DRUG

400 mg/m\^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.

Also known as: calcium folinate, folinic acid, WELLCOVORIN®

Part 2: Pembrolizumab + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Levoleucovorin DRUG

200 mg/m\^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.

Also known as: calcium levofolinate, levofolinic acid, FUSILEV®

Part 2: Pembrolizumab + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Paclitaxel DRUG

175 mg/m\^2 Q3W via IV infusion, as part of investigator's choice TP chemotherapy.

Also known as: TAXOL®, ONXAL®

Part 1: Pembrolizumab + Lenvatinib + Chemotherapy; Part 2: Pembrolizumab + Chemotherapy; Part 2: Pembrolizumab + Lenvatinib + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (198)

City of Hope ( Site 0102)

Duarte, California, 91010, United States

Location

MedStar Washington Hospital Center ( Site 0186)

Washington D.C., District of Columbia, 20010, United States

Location

James Graham Brown Cancer Center ( Site 0117)

Louisville, Kentucky, 40202, United States

Location

Norton Cancer Institute ( Site 0116)

Louisville, Kentucky, 40217, United States

Location

Johns Hopkins Bayview Medical Center ( Site 0152)

Baltimore, Maryland, 21224, United States

Location

UMASS Memorial Medical Center ( Site 0120)

Worcester, Massachusetts, 01655, United States

Location

Capital Health Medical Center - Hopewell ( Site 0189)

Pennington, New Jersey, 08534, United States

Location

Hematology-Oncology Associates of CNY ( Site 0173)

East Syracuse, New York, 13057, United States

Location

Memorial Sloan Kettering Cancer Center ( Site 0132)

New York, New York, 10065, United States

Location

Weill Cornell Medical College ( Site 0133)

New York, New York, 10065, United States

Location

St. Luke's University Health Network ( Site 0185)

Bethlehem, Pennsylvania, 18015, United States

Location

AHN Allegheny General Hospital ( Site 0164)

Pittsburgh, Pennsylvania, 15212, United States

Location

Medical University of South Carolina-Hollings Cancer Center ( Site 0177)

Charleston, South Carolina, 29425, United States

Location

VCU Health Adult Outpatient Pavillion ( Site 0160)

Richmond, Virginia, 23219, United States

Location

Seattle Cancer Care Alliance ( Site 0145)

Seattle, Washington, 98109, United States

Location

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0203)

Berazategui, Buenos Aires, B1884BBF, Argentina

Location

IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)

CABA, Buenos Aires, C1012AAR, Argentina

Location

Instituto de Investigaciones Clinicas Mar del Plata ( Site 0205)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

Location

Fundacion Estudios Clinicos-Oncology ( Site 0215)

Rosario, Santa Fe Province, S2000DEJ, Argentina

Location

Sanatorio Parque ( Site 0206)

Rosario, Santa Fe Province, S2000DSV, Argentina

Location

Hospital Provincial del Centenario ( Site 0217)

Rosario, Santa Fe Province, S2002KDS, Argentina

Location

Fundacion Favaloro ( Site 0201)

Buenos Aires, C1093AAS, Argentina

Location

Fundación Respirar ( Site 0216)

Buenos Aires, C1426ABP, Argentina

Location

Hospital Italiano de Córdoba ( Site 0218)

Córdoba, X5004BAL, Argentina

Location

Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0221)

La Rioja, F5300COE, Argentina

Location

Instituto San Marcos ( Site 0213)

San Juan, J5400EBB, Argentina

Location

CancerCare Manitoba ( Site 0001)

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Princess Margaret Cancer Centre ( Site 0004)

Toronto, Ontario, M5G 2M9, Canada

Location

Hotel-Dieu de Levis ( Site 0013)

Lévis, Quebec, G6V 3Z1, Canada

Location

Fundacion Arturo Lopez Perez FALP ( Site 0403)

Santiago, Region M. de Santiago, 7500836, Chile

Location

Oncovida ( Site 0413)

Santiago, Region M. de Santiago, 7510032, Chile

Location

Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)

Santiago, Region M. de Santiago, 7550000, Chile

Location

Bradford Hill Centro de Investigaciones Clinicas ( Site 0404)

Santiago, Region M. de Santiago, 8420383, Chile

Location

James Lind Centro de Investigacion del Cancer ( Site 0412)

Temuco, Región de la Araucanía, 4800827, Chile

Location

Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0401)

Temuco, Región de la Araucanía, 4810218, Chile

Location

Anhui Provincial Cancer Hospital ( Site 8058)

Hefei, Anhui, 230031, China

Location

The Second Affiliated Hospital of Anhui Medical University ( Site 8026)

Hefei, Anhui, 230031, China

Location

Beijing Cancer Hospital ( Site 8001)

Beijing, Beijing Municipality, 100142, China

Location

Fujian Provincial Cancer Hospital ( Site 8029)

Fuzhou, Fujian, 350014, China

Location

Zhongshan Hospital Affiliated to Xiamen University ( Site 8055)

Xiamen, Fujian, 361004, China

Location

The First Affiliated Hospital of Xiamen University ( Site 8003)

Xiamen City, Fujian Province, Fujian, 361003, China

Location

The First Affiliated Hospital.Sun Yat-sen University ( Site 8047)

Guangzhou, Guangdong, 510080, China

Location

Southern Medical University Nanfang Hospital ( Site 8031)

Guangzhou, Guangdong, 510515, China

Location

The Third Xiangya Hospital of Central South University ( Site 8046)

Changsha, Hainan, 410013, China

Location

The First Affiliated Hospital of Hainan Medical University ( Site 8042)

Haikou, Hainan, 570102, China

Location

Affiliated Hospital of Chengde Medical Univeristy ( Site 8053)

Chengde, Hebei, 067055, China

Location

Harbin Medical University Cancer Hospital ( Site 8009)

Harbin, Heilongjiang, China

Location

Anyang Cancer Hospital ( Site 8006)

Anyang, Henan, 455000, China

Location

The First Affiliated Hospital of Henan University of Science &Technology-Tumor ( Site 8036)

Luoyang, Henan, 471003, China

Location

The First Affiliated Hospital of Xinxiang Medical University ( Site 8018)

Xinxiang, Henan, 453100, China

Location

Tongji Medical College Huazhong Uinversity Of Science and Technology ( Site 8025)

Wuhan, Hubei, 430030, China

Location

Hubei Cancer Hospital ( Site 8014)

Wuhan, Hubei, 430079, China

Location

Affiliated hospital of Jiangnan university ( Site 8049)

Wuxi, Jiangsu, 214122, China

Location

The Affiliated Hospital of Xuzhou Medical University ( Site 8015)

Xuzhou, Jiangsu, 221000, China

Location

Jilin Cancer Hospital ( Site 8016)

Changchun, Jilin, 130012, China

Location

Jinan Central Hospital ( Site 8052)

Jinan, Shandong, 250013, China

Location

Shandong Cancer Hospital ( Site 8060)

Jinan, Shandong, 250117, China

Location

Affiliated Hospital of Jining Medical University ( Site 8017)

Jining, Shandong, 272000, China

Location

Linyi Cancer Hospital- Medical Oncology Department ( Site 8051)

Linyi, Shandong, 276000, China

Location

Shanxi Provincial Cancer Hospital ( Site 8019)

Taiyuan, Shanxi, 030000, China

Location

West China Hospital of Sichuan University ( Site 8048)

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute & Hospital ( Site 8035)

Tianjin, Tianjin Municipality, 300060, China

Location

The Affiliated Cancer Hospital of Xinjiang Medical University. ( Site 8041)

Ürümqi, Xinjiang, 830000, China

Location

Sir Run Run Shaw Hospital ( Site 8021)

Hangzhou, Zhejiang, 310016, China

Location

ICIMED-Oncology Research Unit ( Site 0903)

San José, Provincia de San José, 10108, Costa Rica

Location

PROCLINICAL Pharma ( Site 0904)

San José, Provincia de San José, 11303, Costa Rica

Location

CIMCA Centro de Investigacion y Manejo del Cancer ( Site 0902)

San José, 10103, Costa Rica

Location

Onco Tech S A ( Site 0901)

San José, 10103, Costa Rica

Location

Rigshospitalet ( Site 2102)

Copenhagen, Capital Region, 2100, Denmark

Location

Odense University Hospital ( Site 2101)

Odense, Region Syddanmark, 5000, Denmark

Location

Institut De Cancerologie De Lorraine ( Site 1010)

Vandœuvre-lès-Nancy, Ain, 54519, France

Location

Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1014)

Strasbourg, Alsace, 67200, France

Location

Centre François Baclesse ( Site 1009)

Caen, Calvados, 14076, France

Location

Centre Georges Francois Leclerc ( Site 1008)

Dijon, Cote-d Or, 21000, France

Location

C.H. regional Unv. de Brest - Hopital La Cavale Blanche - Institut de Cancerologie et d Imagerie ( S

Brest, Finistere, 29200, France

Location

CHU Besançon ( Site 1015)

Besançon, Franche-Comte, 25000, France

Location

CHU Bordeaux Haut-Leveque ( Site 1012)

Pessac, Gironde, 33604, France

Location

Institut du Cancer de Montpellier ( Site 1002)

Montpellier, Herault, 34298, France

Location

CHRU de Tours - Hopital Bretonneau ( Site 1018)

Tours, Indre-et-Loire, 37044, France

Location

Institut De Cancerologie De L Ouest ( Site 1003)

Saint-Herblain, Loire-Atlantique, 44805, France

Location

Hôpital Claude Huriez ( Site 1030)

Lille, Nord, 59000, France

Location

Hopital Henri Mondor ( Site 1007)

Créteil, Val-de-Marne, 94010, France

Location

Hopital Saint Louis ( Site 1029)

Paris, 75010, France

Location

Centro Regional de Sub Especialidades Medicas SA ( Site 0604)

Guatemala, Departamento de Quetzaltenango, 09001, Guatemala

Location

MEDI-K ( Site 0601)

Guatemala City, 01009, Guatemala

Location

Oncomedica ( Site 0602)

Guatemala City, 01010, Guatemala

Location

Soluciones Gastrointestinales S.A. ( Site 0607)

Guatemala City, 01010, Guatemala

Location

Queen Mary Hospital ( Site 4001)

Hong Kong, Hong Kong

Location

Queen Elizabeth Hospital. ( Site 4004)

Kowloon, Hong Kong

Location

Pecsi Tudomanyegyetem AOK ( Site 1204)

Pécs, Baranya, 7624, Hungary

Location

Petz Aladar Egyetemi Oktato Korhaz ( Site 1210)

Győr, Győr-Moson-Sopron, 9024, Hungary

Location

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1203)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Orszagos Onkologiai Intezet ( Site 1207)

Budapest, 1122, Hungary

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 1313)

Meldola, Emilia-Romagna, 47014, Italy

Location

A.O.U. Santa Maria della Misericordia di Udine ( Site 1302)

Udine, Friuli Venezia Giulia, 33100, Italy

Location

Humanitas Research Hospital ( Site 1309)

Rozzano, Lombardy, 20089, Italy

Location

Azienda Ospedaliera Universitaria Pisana ( Site 1312)

Pisa, Tuscany, 56126, Italy

Location

Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 1311)

Padua, Veneto, 35128, Italy

Location

Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1314)

Catanzaro, 88100, Italy

Location

Azienda Ospedaliero Universitaria Careggi ( Site 1301)

Florence, 50134, Italy

Location

IRCCS Ospedale San Raffaele di Milano ( Site 1304)

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1306)

Milan, 20133, Italy

Location

A.O. Universitaria di Modena ( Site 1307)

Modena, 41124, Italy

Location

A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1305)

Naples, 80131, Italy

Location

Universita Cattolica del Sacro Cuore - Policlinico Gemelli ( Site 1310)

Roma, 00168, Italy

Location

Aichi Cancer Center Hospital ( Site 9006)

Nagoya, Aichi-ken, 464-8681, Japan

Location

Chiba Cancer Center ( Site 9023)

Chiba, Chiba, 260-8717, Japan

Location

National Cancer Center Hospital East ( Site 9002)

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center ( Site 9019)

Matsuyama, Ehime, 791-0280, Japan

Location

Hyogo Cancer Center ( Site 9014)

Akashi, Hyōgo, 673-8558, Japan

Location

Ibaraki Prefectural Central Hospital ( Site 9007)

Kasama, Ibaraki, 309-1793, Japan

Location

Kagawa University Hospital ( Site 9015)

Kita-gun, Kagawa-ken, 761-0793, Japan

Location

Kanagawa Cancer Center ( Site 9004)

Yokohama, Kanagawa, 241-8515, Japan

Location

Tohoku University Hospital ( Site 9013)

Sendai, Miyagi, 980-8574, Japan

Location

Niigata Cancer Center Hospital ( Site 9022)

Niigata, Niigata, 951-8566, Japan

Location

Kindai University Hospital ( Site 9017)

Sayama, Osaka, 589-8511, Japan

Location

Osaka University Hospital ( Site 9021)

Suita, Osaka, 565-0871, Japan

Location

Osaka Medical and Pharmaceutical University Hospital ( Site 9008)

Takatsuki, Osaka, 569-8686, Japan

Location

Saitama Prefectural Cancer Center ( Site 9003)

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center ( Site 9016)

Nakatogari, Shizuoka, 411-8777, Japan

Location

Tokyo Metropolitan Komagome Hospital ( Site 9028)

Bunkyo Ku, Tokyo, 113-8677, Japan

Location

Toranomon Hospital ( Site 9026)

Minato-ku, Tokyo, 105-8470, Japan

Location

Showa University Hospital ( Site 9025)

Shinagawa, Tokyo, 142-8666, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 9010)

Fukuoka, 811-1395, Japan

Location

University Hospital,Kyoto Prefectural University of Medicine ( Site 9027)

Kyoto, 602-8566, Japan

Location

Kyoto University Hospital ( Site 9011)

Kyoto, Japan

Location

Okayama University Hospital ( Site 9024)

Okayama, 700-8558, Japan

Location

Osaka International Cancer Institute ( Site 9009)

Osaka, 541-8567, Japan

Location

Osaka General Medical Center ( Site 9018)

Osaka, 558-8558, Japan

Location

National Cancer Center Hospital ( Site 9001)

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR ( Site 9005)

Tokyo, 135-8550, Japan

Location

Keio University Hospital ( Site 9020)

Tokyo, 160-8582, Japan

Location

University Malaya Medical Centre ( Site 9101)

Lembah Pantai, Kuala Lumpur, 59100, Malaysia

Location

Sarawak General Hospital-Radiotherapy Unit ( Site 9100)

Kuching, Sarawak, 93586, Malaysia

Location

Hospital Kuala Lumpur ( Site 9104)

Kuala Lumpur, 50586, Malaysia

Location

MEMORIAL HEALTHCARE INTERNATIONAL S.R.L. ( Site 2201)

Bucharest, București, 013812, Romania

Location

Cardiomed SRL Cluj-Napoca-Medical Oncology ( Site 2207)

Cluj-Napoca, Cluj, 400015, Romania

Location

SC Radiotherapy Center Cluj SRL ( Site 2202)

Comuna Floresti, Cluj, 407280, Romania

Location

Ovidius Clinical Hospital OCH-Oncology and Hematology ( Site 2203)

Ovidiu, Constanța County, 905900, Romania

Location

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2204)

Craiova, Dolj, 200542, Romania

Location

Policlinica Oncomed SRL ( Site 2206)

Timișoara, Timiș County, 300239, Romania

Location

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)

Ufa, Baskortostan, Respublika, 450054, Russia

Location

GBUZ LOKB ( Site 1502)

Saint-Petersburg, Leningradskaya Oblast', 194291, Russia

Location

FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1510)

Moscow, Moscow, 115478, Russia

Location

Academician I.P. Pavlov First St. Petersburg State Medical University ( Site 1519)

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1503)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Republican Clinical Oncology Dispensary of Tatarstan MoH named after professor M.Z. Sigal ( Site 150

Kazan', Tatarstan, Respublika, 420029, Russia

Location

SAIH of Tyumen reg "Multifield clinical medical center "Medical city" ( Site 1520)

Tyumen, Tyumen Oblast, 625041, Russia

Location

National Cancer Centre Singapore ( Site 9201)

Singapore, Central Singapore, 168583, Singapore

Location

Wits Clinical Research ( Site 9502)

Johannesburg, Gauteng, 2193, South Africa

Location

The Oncology Centre ( Site 9505)

Durban, KwaZulu-Natal, 4091, South Africa

Location

Seoul National University Bundang Hospital ( Site 5006)

Seongnam-si, Kyonggi-do, 13605, South Korea

Location

Asan Medical Center ( Site 5002)

Songpagu, Seoul, 05505, South Korea

Location

Severance Hospital ( Site 5003)

Seoul, 03722, South Korea

Location

Samsung Medical Center ( Site 5005)

Seoul, 06351, South Korea

Location

Korea University Guro Hospital ( Site 5001)

Seoul, 08308, South Korea

Location

Hospital Universitario Marques de Valdecilla ( Site 1602)

Santander, Cantabria, 39008, Spain

Location

Complexo Hospitalario Universitario de Ourense-MEDICAL ONCOLOGY ( Site 1609)

Ourense, Orense, 32005, Spain

Location

Hospital Universitario General de Asturias ( Site 1601)

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital General Universitari Vall d Hebron ( Site 1607)

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Maranon ( Site 1604)

Madrid, 28007, Spain

Location

Hospital Virgen del Rocio ( Site 1606)

Seville, 41013, Spain

Location

Chi Mei Hospital - Liouying Branch-Clinical Trial Center ( Site 6007)

Tainan, Tainan, 73657, Taiwan

Location

Chang Gung Med Foundation. Kaohsiung Branch ( Site 6005)

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital ( Site 6003)

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital ( Site 6004)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 6001)

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital ( Site 6006)

Taipei, 11217, Taiwan

Location

Faculty of Medicine Siriraj Hospital ( Site 7002)

Bangkok, Bangkok, 10700, Thailand

Location

Songklanagarind hospital ( Site 7001)

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 1714)

Adana, 01140, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1701)

Ankara, 06230, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi ( Site 1702)

Ankara, 06520, Turkey (Türkiye)

Location

Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 1715)

Ankara, 06800, Turkey (Türkiye)

Location

Atatürk Üniversitesi-onkoloji ( Site 1712)

Erzurum, 25070, Turkey (Türkiye)

Location

Acibadem Universitesi Atakent Hastanesi-Medical Oncology ( Site 1716)

Istanbul, 34303, Turkey (Türkiye)

Location

Istanbul Okmeydanı Egitim ve Arastirma Hastanesi ( Site 1711)

Istanbul, 34384, Turkey (Türkiye)

Location

Medeniyet Universitesi Tip Fakultesi ( Site 1703)

Istanbul, 34732, Turkey (Türkiye)

Location

Chernihiv Medical Center of Modern Oncology ( Site 1811)

Chernihiv, Chernihiv Oblast, 14029, Ukraine

Location

Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center" ( Site 1819)

Chernivtsi, Chernivetska Oblast, 58013, Ukraine

Location

MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council ( Site 1804)

Kryviy Rih, Dnipropetrovsk Oblast, 50048, Ukraine

Location

Kharkiv Regional Clinical Oncology Center ( Site 1812)

Kharkiv, Kharkivs’ka Oblast’, 61000, Ukraine

Location

Institute of General and Emergency Surgery n.a Zaitsev NAMS of Ukraine ( Site 1813)

Kharkiv, Kharkivs’ka Oblast’, 61103, Ukraine

Location

Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (

Antonivka Village, Kherson Oblast, 73000, Ukraine

Location

SNPE National Cancer Institute ( Site 1806)

Kyiv, Kyivska Oblast, 03022, Ukraine

Location

Rivne Regional Clinical Hospital ( Site 1817)

Rivne, Rivne Oblast, 33007, Ukraine

Location

Podillya Regional Center of Oncology ( Site 1809)

Vinnytsia, Vinnytsia Oblast, 21029, Ukraine

Location

Volyn Regional Oncological Dispensary ( Site 1816)

Lutsk, Volyn Oblast, 43018, Ukraine

Location

Shalimov Institute of Surgery and Transplantation ( Site 1818)

Kyiv, 03126, Ukraine

Location

Cambridge University Hospitals NHSFT ( Site 1908)

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Ninewells Hospital and Medical School ( Site 1907)

Dundee, Dundee City, DD2 1SG, United Kingdom

Location

Nottingham University Hospital NHS Trust ( Site 1910)

Nottingham, England, NG5 1PF, United Kingdom

Location

St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1915)

London, London, City of, EC1A 7BE, United Kingdom

Location

University College London Hospitals NHS Foundation Trust ( Site 1901)

London, London, City of, NW1 2BU, United Kingdom

Location

Royal Marsden NHS Foundation Trust ( Site 1905)

London, London, City of, SW3 6JJ, United Kingdom

Location

Royal Marsden NHS Trust. ( Site 1906)

Sutton, London, City of, SM2 5PT, United Kingdom

Location

Western General Hospital ( Site 1912)

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

The Christie NHS Foundation Trust ( Site 1909)

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38695479 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib; Cisplatin; Fluorouracil; Oxaliplatin; Leucovorin; Levoleucovorin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: July 2, 2021
• Study Start: July 28, 2021
• Primary Completion: May 8, 2025
• Study Completion (Estimated): June 12, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CL (6); FR (13); TW (6); TH (2); CA (3); GU (4); DK (2); KR (5); ES (6); TU (8); UA (11); AR (11); GB (9); US (15); CN (29); HK (2); CO (4); IT (12); JP (27); RU (7); SG (1); ZA (2); HU (4); MY (3); RO (6)