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)
Metastatic Esophageal Squamous Cell Carcinoma
About this trial
This is an interventional treatment trial for Metastatic Esophageal Squamous Cell Carcinoma focused on measuring programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- City of Hope ( Site 0102)
- MedStar Washington Hospital Center ( Site 0186)Recruiting
- James Graham Brown Cancer Center ( Site 0117)Recruiting
- Norton Cancer Institute ( Site 0116)Recruiting
- Johns Hopkins Bayview Medical Center ( Site 0152)Recruiting
- UMASS Memorial Medical Center ( Site 0120)Recruiting
- Hematology-Oncology Associates of CNY ( Site 0173)Recruiting
- Memorial Sloan Kettering Cancer Center ( Site 0132)Recruiting
- Weill Cornell Medical College ( Site 0133)Recruiting
- AHN Allegheny General Hospital ( Site 0164)Recruiting
- VCU Health Adult Outpatient Pavillion ( Site 0160)Recruiting
- Seattle Cancer Care Alliance ( Site 0145)Recruiting
- Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0203)Recruiting
- IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)Recruiting
- Instituto de Investigaciones Clinicas Mar del Plata ( Site 0205)Recruiting
- Fundacion Estudios Clinicos-Oncology ( Site 0215)Recruiting
- Sanatorio Parque ( Site 0206)Recruiting
- Hospital Provincial del Centenario ( Site 0217)Recruiting
- Fundacion Favaloro ( Site 0201)Recruiting
- Fundación Respirar ( Site 0216)Recruiting
- Hospital Italiano de Córdoba ( Site 0218)Recruiting
- Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0221)Recruiting
- Instituto San Marcos ( Site 0213)Recruiting
- Princess Margaret Cancer Centre ( Site 0004)Recruiting
- Hotel-Dieu de Levis ( Site 0013)Recruiting
- James Lind Centro de Investigación del Cáncer ( Site 0412)Recruiting
- Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0401)Recruiting
- Fundacion Arturo Lopez Perez FALP ( Site 0403)Recruiting
- Oncovida ( Site 0413)Recruiting
- Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)Recruiting
- Bradford Hill Centro de Investigaciones Clinicas ( Site 0404)Recruiting
- Anhui Cancer Hospital ( Site 8058)Recruiting
- The Second Affiliated Hospital of Anhui Medical University ( Site 8026)Recruiting
- Beijing Cancer Hospital ( Site 8001)Recruiting
- Fujian Provincial Cancer Hospital ( Site 8029)Recruiting
- The First Affiliated Hospital of Xiamen University ( Site 8003)Recruiting
- Zhongshan Hospital Affiliated to Xiamen University ( Site 8055)Recruiting
- The First Affiliated Hospital.Sun Yat-sen University ( Site 8047)Recruiting
- Southern Medical University Nanfang Hospital ( Site 8031)Recruiting
- The Third Xiangya Hospital of Central South University ( Site 8046)Recruiting
- The First Affiliated Hospital of Hainan Medical University ( Site 8042)Recruiting
- Affiliated Hospital of Chengde Medical Univeristy ( Site 8053)Recruiting
- Harbin Medical University Cancer Hospital ( Site 8009)Recruiting
- Anyang Cancer Hospital ( Site 8006)Recruiting
- The First Affiliated Hospital of Henan University of Science &Technology-Tumor ( Site 8036)Recruiting
- The First Affiliated Hospital of Xinxiang Medical University ( Site 8018)Recruiting
- Tongji Medical College Huazhong Uinversity Of Science and Technology ( Site 8025)Recruiting
- Hubei Cancer Hospital ( Site 8014)Recruiting
- Affiliated hospital of Jiangnan university ( Site 8049)Recruiting
- The Affiliated Hospital of Xuzhou Medical University ( Site 8015)Recruiting
- Jilin Cancer Hospital ( Site 8016)Recruiting
- Jinan Central Hospital ( Site 8052)Recruiting
- Shandong Cancer Hospital ( Site 8060)Recruiting
- Affiliated Hospital of Jining Medical University ( Site 8017)Recruiting
- Linyi Cancer Hospital- Medical Oncology Department ( Site 8051)Recruiting
- Shanxi Provincial Cancer Hospital ( Site 8019)Recruiting
- West China Hospital of Sichuan University ( Site 8048)Recruiting
- Tianjin Medical University Cancer Institute & Hospital ( Site 8035)Recruiting
- Cancer Hospital Affiliated to Xinjiang Medical University ( Site 8041)Recruiting
- Sir Run Run Shaw Hospital ( Site 8021)Recruiting
- ICIMED-Oncology Research Unit ( Site 0903)Recruiting
- PROCLINICAL Pharma ( Site 0904)Recruiting
- CIMCA Centro de Investigacion y Manejo del Cancer ( Site 0902)Recruiting
- Onco Tech S A ( Site 0901)Recruiting
- Rigshospitalet ( Site 2102)Recruiting
- Odense University Hospital ( Site 2101)Recruiting
- Institut De Cancerologie De Lorraine ( Site 1010)Recruiting
- Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1014)Recruiting
- Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologiRecruiting
- Centre François Baclesse ( Site 1009)Recruiting
- Centre Georges Francois Leclerc ( Site 1008)Recruiting
- CHU Besançon ( Site 1015)Recruiting
- CHU Bordeaux Haut-Leveque ( Site 1012)Recruiting
- Institut du Cancer de Montpellier ( Site 1002)Recruiting
- CHRU de Tours - Hopital Bretonneau ( Site 1018)Recruiting
- Institut De Cancerologie De L Ouest ( Site 1003)Recruiting
- Hôpital Claude Huriez ( Site 1030)Recruiting
- Hopital Henri Mondor ( Site 1007)Recruiting
- Hopital Saint Louis ( Site 1029)Recruiting
- Centro Regional de Sub Especialidades Medicas SA ( Site 0604)Recruiting
- Oncomedica ( Site 0602)Recruiting
- Soluciones Gastrointestinales S.A. ( Site 0607)
- Medi-K Cayala ( Site 0601)Recruiting
- Queen Mary Hospital ( Site 4001)Recruiting
- Queen Elizabeth Hospital. ( Site 4004)Recruiting
- Pecsi Tudomanyegyetem AOK ( Site 1204)Recruiting
- Petz Aladar Egyetemi Oktato Korhaz ( Site 1210)Recruiting
- Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1203)Recruiting
- Orszagos Onkologiai Intezet ( Site 1207)Recruiting
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 1313)Recruiting
- A.O.U. Santa Maria della Misericordia di Udine ( Site 1302)Recruiting
- IRCCS Ospedale San Raffaele di Milano ( Site 1304)Recruiting
- Humanitas Research Hospital ( Site 1309)Recruiting
- Azienda Ospedaliera Universitaria Pisana ( Site 1312)Recruiting
- Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1314)Recruiting
- Azienda Ospedaliero Universitaria Careggi ( Site 1301)Recruiting
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1306)Recruiting
- A.O. Universitaria di Modena ( Site 1307)Recruiting
- A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1305)Recruiting
- Universita Cattolica del Sacro Cuore - Policlinico Gemelli ( Site 1310)Recruiting
- Aichi Cancer Center Hospital ( Site 9006)Recruiting
- Chiba cancer center ( Site 9023)Recruiting
- National Cancer Center Hospital East ( Site 9002)Recruiting
- National Hospital Organization Shikoku Cancer Center ( Site 9019)Recruiting
- Hyogo Cancer Center ( Site 9014)Recruiting
- Ibaraki Prefectural Central Hospital ( Site 9007)Recruiting
- Kagawa University Hospital ( Site 9015)Recruiting
- Kanagawa Cancer Center ( Site 9004)Recruiting
- Tohoku University Hospital ( Site 9013)Recruiting
- Kindai University Hospital- Osakasayama Campus ( Site 9017)Recruiting
- Osaka University Hospital ( Site 9021)Recruiting
- Osaka Medical and Pharmaceutical University Hospital ( Site 9008)Recruiting
- Saitama Cancer Center ( Site 9003)Recruiting
- Shizuoka Cancer Center ( Site 9016)Recruiting
- Showa University Hospital ( Site 9025)Recruiting
- National Hospital Organization Kyushu Cancer Center ( Site 9010)Recruiting
- Kyoto University Hospital ( Site 9011)Recruiting
- Okayama University Hospital ( Site 9024)Recruiting
- Osaka International Cancer Institute ( Site 9009)Recruiting
- Osaka General Medical Center ( Site 9018)Recruiting
- National Cancer Center Hospital ( Site 9001)Recruiting
- The Cancer Institute Hospital of JFCR ( Site 9005)Recruiting
- Keio university hospital ( Site 9020)Recruiting
- Seoul National University Bundang Hospital ( Site 5006)Recruiting
- Asan Medical Center ( Site 5002)Recruiting
- Severance Hospital ( Site 5003)Recruiting
- Samsung Medical Center ( Site 5005)Recruiting
- Korea University Guro Hospital ( Site 5001)Recruiting
- University Malaya Medical Centre ( Site 9101)Recruiting
- SC Radiotherapy Center Cluj SRL ( Site 2202)Recruiting
- Ovidius Clinical Hospital OCH-Oncology and Hematology ( Site 2203)Recruiting
- S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2204)Recruiting
- Policlinica Oncomed SRL ( Site 2206)Recruiting
- S.C.Focus Lab Plus S.R.L ( Site 2201)Recruiting
- Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)
- FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1510)
- SBHI Leningrad Regional Oncology Dispensary ( Site 1502)
- Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1503)
- Academician I.P. Pavlov First St. Petersburg State Medical University ( Site 1519)
- Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1509)
- SAIH of Tyumen reg "Multifield clinical medical center "Medical city" ( Site 1520)
- National Cancer Centre Singapore ( Site 9201)Recruiting
- The Oncology Centre ( Site 9505)Recruiting
- Hospital Universitario General de Asturias ( Site 1601)Recruiting
- Hospital Universitario Marques de Valdecilla ( Site 1602)Recruiting
- Complexo Hospitalario Universitario de Ourense-MEDICAL ONCOLOGY ( Site 1609)Recruiting
- Hospital General Universitari Vall d Hebron ( Site 1607)Recruiting
- Hospital General Universitario Gregorio Maranon ( Site 1604)Recruiting
- Hospital Virgen del Rocio ( Site 1606)Recruiting
- Chi Mei Hospital - Liouying Branch-Clinical Trial Center ( Site 6007)Recruiting
- Chang Gung Med Foundation. Kaohsiung Branch ( Site 6005)Recruiting
- China Medical University Hospital ( Site 6003)Recruiting
- National Cheng Kung University Hospital ( Site 6004)Recruiting
- National Taiwan University Hospital ( Site 6001)Recruiting
- Taipei Veterans General Hospital ( Site 6006)Recruiting
- Medeniyet Universitesi Tip Fakultesi ( Site 1703)Recruiting
- Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1701)Recruiting
- Memorial Ankara Hastanesi ( Site 1702)Recruiting
- Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 1712)Recruiting
- Istanbul Okmeydanı Egitim ve Arastirma Hastanesi ( Site 1711)
- Chernihiv Medical Center of Modern Oncology ( Site 1811)
- MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council ( Site 1804)
- Kharkiv Regional Clinical Oncology Center ( Site 1812)
- Institute of General and Emergency Surgery n.a Zaitsev NAMS of Ukraine ( Site 1813)
- Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (
- National Cancer Institute of the MoH of Ukraine ( Site 1806)
- Podillya Regional Center of Oncology ( Site 1809)
- Volyn Regional Oncological Dispensary ( Site 1816)
- Cambridge University Hospitals NHSFT ( Site 1908)Recruiting
- Ninewells Hospital and Medical School ( Site 1907)Recruiting
- Nottingham University Hospital NHS Trust ( Site 1910)Recruiting
- St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1915)Recruiting
- University College London Hospitals NHS Foundation Trust ( Site 1901)Recruiting
- Royal Marsden NHS Foundation Trust ( Site 1905)Recruiting
- Royal Marsden NHS Trust. ( Site 1906)Recruiting
- Western General Hospital ( Site 1912)Recruiting
- The Christie NHS Foundation Trust ( Site 1909)Recruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Pembrolizumab + Lenvatinib + Chemotherapy
Pembrolizumab + Chemotherapy
Participants receive pembrolizumab intravenously (IV) plus lenvatinib orally in combination with FP or TP in Part 1, or in combination with investigator's choice of chemotherapy with FP IV or TP IV or oxaliplatin, 5-FU and leucovorin (mFOLFOX6) IV in Part 2. Induction consists of pembrolizumab 400 mg once every 6-weeks (Q6W) for up to ~12 weeks plus lenvatinib 8 mg once daily (QD) for up to ~12 weeks 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) once every 3 weeks (Q3W) for up to ~12 weeks 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 up to ~12 weeks). This is followed by consolidation with pembrolizumab 400 mg Q6W for up to 16 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) plus lenvatinib 20 mg QD until progressive disease or discontinuation.
Participants receive pembrolizumab 400 mg IV Q6W for up to 18 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) in combination with investigator's choice of 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]), during Part 2.