Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015) (LEAP-015)

Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy Compared With Standard of Care Therapy as First-line Intervention in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (LEAP-015)

The purpose of this study is to assess the efficacy and safety of lenvatinib (E7080/MK-7902) plus pembrolizumab (MK-3475) plus chemotherapy compared with chemotherapy alone in participants with advanced/metastatic gastroesophageal cancer.

The primary study hypotheses are that lenvatinib plus pembrolizumab plus chemotherapy is superior to chemotherapy alone for both overall survival (OS) and 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 participants with programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 and in all participants.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced/Metastatic Gastroesophageal Adenocarcinoma
• Intervention / Treatment: Biological: Pembrolizumab; Biological: Lenvatinib; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Leucovorin (or Levoleucovorin); Drug: 5-FU

Detailed Description

There will be 2 parts to the study: a Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (Safety Run-in), approximately 12 participants will be treated with lenvatinib in combination with pembrolizumab and chemotherapy with either capecitabine and oxaliplatin (CAPOX), or 5-fluorouracil (5-FU), Leucovorin, and oxaliplatin (mFOLFOX6). Participants will be closely followed for dose-limiting toxicities for 21 days after the first dose of study intervention.

In Part 2, up to 878 eligible participants (not including those participating in Part 1) will be randomly assigned in a 1:1 ratio to either lenvatinib plus pembrolizumab plus chemotherapy (CAPOX or mFOLFOX6) or Chemotherapy alone (CAPOX or mFOLFOX6).

Participants can receive up to 18 infusions (up to 2 years) of pembrolizumab in the first course. Participants may be eligible to receive a second course of pembrolizumab (approximately 1 year) at the investigator's discretion.

• Study Type: Interventional
• Enrollment (Estimated): 890
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1093AAS
    • Fundacion Favaloro ( Site 0201)
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman ( Site 0210)
  • Buenos Aires, Argentina, C1264AAA
    • Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0207)
  • Buenos Aires, Argentina, C1431FWO
    • CEMIC ( Site 0209)
  • Cordoba, Argentina, X5016KEH
    • Hospital Privado de Cordoba ( Site 0204)
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1012AAR
      • IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Instituto Medico Alexander Fleming ( Site 0208)
• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital ( Site 2305)
    • Wollongong, New South Wales, Australia, 2500
      • Wollongong Hospital ( Site 2307)
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women s Hospital ( Site 2304)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Hollywood Private Hospital-Medical Oncology ( Site 2308)
• Belgium
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • CHU UCL Namur Site de Godinne ( Site 1005)
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent ( Site 1002)
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven ( Site 1004)
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • AZ Delta ( Site 1006)
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre ( Site 0101)
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Site ( Site 0106)
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, Temuco
      • Centro Investigación del Cáncer James Lind ( Site 0414)
  • Coquimbo
    • La Serena, Coquimbo, Chile, 1720430
      • IC La Serena Research ( Site 0410)
  • Maule
    • Talca, Maule, Chile, 3460000
      • Clinica Universidad Catolica del Maule ( Site 0411)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7500836
      • Fundacion Arturo Lopez Perez FALP ( Site 0403)
    • Santiago, Region M. De Santiago, Chile, 7550000
      • Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Bradfordhill ( Site 0404)
• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital ( Site 2415)
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences ( Site 2403)
    • Beijing, Beijing, China, 100035
      • Beijing Cancer Hospital ( Site 2453)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital ( Site 2408)
    • Fuzhou, Fujian, China, 350025
      • The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University ( Site 2420)
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University ( Site 2446)
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Affiliated to Xiamen University ( Site 2421)
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • First Hospital of Lanzhou University ( Site 2417)
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Nanfang Hospital ( Site 2456)
  • Hainan
    • Haikou, Hainan, China, 570102
      • The Affiliated Hospital Of Hainan Medical University-Cancer rehabilitation and palliative treatment
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Fourth Hospital Of Hebei Medical University ( Site 2441)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital ( Site 2410)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 2443)
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital ( Site 2429)
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital ( Site 2440)
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Cancer Hospital-Department of Oncology ( Site 2458)
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital ( Site 2419)
    • Nantong, Jiangsu, China, 226361
      • Nantong Tumor Hospital-Digestive Oncology ( Site 2464)
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital ( Site 2438)
  • Shaanxi
    • XI An, Shaanxi, China, 710038
      • Tang Du Hospital ( Site 2432)
  • Shandong
    • Linyi, Shandong, China, 276000
      • LinYi Cancer Hospital-Gastrology department ( Site 2463)
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital ( Site 2424)
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital ( Site 2455)
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital ( Site 2447)
  • Xinjiang
    • Urumqi, Xinjiang, China, 830011
      • Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2428)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital ( Site 2412)
    • Hangzhou, Zhejiang, China, 310009
      • The First Affiliated Hospital of Zhejiang University ( Site 2414)
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Clinica de la Costa S.A.S. ( Site 0502)
  • Cesar
    • Valledupar, Cesar, Colombia, 200001
      • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0508)
  • Cordoba
    • Monteria, Cordoba, Colombia, 230002
      • Oncomedica S.A. ( Site 0507)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 111321
      • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0501)
  • Narino
    • Pasto, Narino, Colombia, 520001
      • Instituto Cancerologico de Narino Ltda ( Site 0504)
  • Risaralda
    • Pereira, Risaralda, Colombia, 660001
      • Oncologos del Occidente S.A. ( Site 0525)
• Costa Rica
  • San Jose
    • San José, San Jose, Costa Rica, 10103
      • CIMCA-Hemato-Oncology ( Site 0601)
    • Santa Ana, San Jose, Costa Rica, 10903
      • Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0602)
• France
  • Paris, France, 75010
    • Hopital Saint Louis ( Site 1100)
  • Paris, France, 75012
    • CHU Hopital Saint Antoine ( Site 1102)
  • Calvados
    • Caen, Calvados, France, 14076
      • Centre Francois Baclesse ( Site 1107)
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21079
      • Centre Georges Francois Leclerc ( Site 1106)
  • Gironde
    • Pessac, Gironde, France, 33604
      • CHU Bordeaux Haut-Leveque ( Site 1110)
  • Haute-Savoie
    • Epagny Metz-Tessy, Haute-Savoie, France, 74370
      • Centre Hospitalier Annecy Genevois ( Site 1117)
  • Pays-de-la-Loire
    • Nantes, Pays-de-la-Loire, France, 44093
      • CHU Hotel Dieu Nantes ( Site 1101)
  • Rhone-Alpes
    • Lyon, Rhone-Alpes, France, 69003
      • Hôpital Edouard Herriot ( Site 1116)
  • Val-de-Marne
    • Creteil, Val-de-Marne, France, 94010
      • Hopital Henri Mondor ( Site 1105)
  • Vaucluse
    • Avignon, Vaucluse, France, 84918
      • Institut du Cancer Avignon-Provence ( Site 1103)
• Germany
  • Berlin, Germany, 13353
    • Charite Berlin Campus Virchow-Klinikum ( Site 1202)
  • Hamburg, Germany, 20249
    • Facharztzentrum Eppendorf ( Site 1201)
  • Bayern
    • Muechen, Bayern, Germany, 81675
      • Klinikum Rechts der Isar der TU Muenchen ( Site 1200)
    • Regensburg, Bayern, Germany, 93053
      • Universitaetsklinikum Regensburg ( Site 1203)
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60488
      • Krankenhaus Nordwest ( Site 1205)
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover ( Site 1210)
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitaetsklinikum Leipzig ( Site 1211)
• Guatemala
  • Guatemala, Guatemala, 01010
    • Clinica Privada Dr Rixci Ramirez Fallas ( Site 0702)
  • Guatemala, Guatemala, 01010
    • Oncologika S.A. ( Site 0704)
  • Guatemala, Guatemala, 01010
    • Oncomedica ( Site 0701)
  • Guatemala, Guatemala, 01010
    • Soluciones Gastrointestinales S.A. ( Site 0706)
  • Guatemala, Guatemala, 01015
    • Sanatorio Nuestra Senora del Pilar ( Site 0705)
  • Guatemala, Guatemala, 01016
    • Medi-K Cayala ( Site 0700)
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital ( Site 2503)
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital. ( Site 2502)
  • Hong Kong, Hong Kong
    • Queen Mary Hospital ( Site 2501)
• Ireland
  • Dublin, Ireland, Dublin 9
    • Beaumont Hospital ( Site 1402)
  • Leinster
    • Dublin, Leinster, Ireland, Dublin 8
      • St James Hospital ( Site 1400)
• Israel
  • Be'er Sheva, Israel, 8410101
    • Soroka Medical Center ( Site 1507)
  • Hadera, Israel, 3810004
    • Hillel Yaffe Medical Center ( Site 1503)
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology Division ( Site 1502)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 1501)
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center ( Site 1504)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 1506)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 1500)
• Italy
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1611)
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele di Milano ( Site 1603)
  • Napoli, Italy, 80131
    • A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1604)
  • Abruzzo
    • Meldola, Abruzzo, Italy, 47014
      • Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1608)
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • Presidio Ospedaliero Universitario Santa Maria della Misericordia ( Site 1609)
  • Lombardia
    • Milan, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1610)
    • Rozzano, Lombardia, Italy, 20089
      • Humanitas Research Hospital ( Site 1600)
  • Veneto
    • Vicenza, Veneto, Italy, 36100
      • AULSS8 Berica-Ospedale S.Bortolo ( Site 1607)
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 2609)
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital ( Site 2612)
  • Osaka, Japan, 5418567
    • Osaka International Cancer Institute ( Site 2607)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 2602)
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR ( Site 2605)
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 2603)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 2601)
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center ( Site 2610)
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 2621)
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital ( Site 2606)
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital ( Site 2618)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 2611)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 2608)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 2622)
    • Osakasayama, Osaka, Japan, 5898511
      • Kindai University Hospital ( Site 2600)
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Cancer Center ( Site 2604)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 2803)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 2800)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 2801)
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital ( Site 2805)
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital ( Site 2808)
  • Kyonggi-do
    • Anyang-si, Kyonggi-do, Korea, Republic of, 14068
      • Hallym University Sacred Heart Hospital ( Site 2806)
    • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 2804)
  • Seoul
    • Songpagu, Seoul, Korea, Republic of, 05505
      • Asan Medical Center ( Site 2802)
  • Taejon-Kwangyokshi
    • Daejeon, Taejon-Kwangyokshi, Korea, Republic of, 35365
      • Konyang University ( Site 2807)
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 53-413
      • Dolnoslaskie Centrum Onkologii. ( Site 1712)
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-034
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1704)
  • Podkarpackie
    • Przemysl, Podkarpackie, Poland, 37-700
      • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1702)
  • Wielkopolskie
    • Konin, Wielkopolskie, Poland, 62-500
      • Przychodnia Lekarska KOMED ( Site 1701)
    • Poznan, Wielkopolskie, Poland, 60-780
      • Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 1703)
• Russian Federation
  • Chelyabinskaya Oblast
    • Chelyabinsk, Chelyabinskaya Oblast, Russian Federation, 454087
      • Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1816)
  • Moskva
    • Moscow, Moskva, Russian Federation, 105203
      • National Medical and Surgical Center n.a.N.I.Pirogov ( Site 1805)
    • Moscow, Moskva, Russian Federation, 115478
      • Blokhin National Medical Oncology ( Site 1800)
    • Moscow, Moskva, Russian Federation, 121359
      • Central Clinical Hospital with Polyclinic ( Site 1801)
  • Samarskaya Oblast
    • Samara, Samarskaya Oblast, Russian Federation, 443011
      • Medical University REAVIZ ( Site 1814)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 198255
      • St Petersburg City Clinical Oncology Dispensary ( Site 1808)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 188663
      • Leningrad Regional Oncology Center ( Site 1810)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1809)
  • Yaroslavskaya Oblast
    • Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150054
      • Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1821)
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d Hebron ( Site 1907)
  • Madrid, Spain, 28007
    • Hospital General Gregorio Maranon de Madrid ( Site 1904)
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario General de Asturias ( Site 1901)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla ( Site 1902)
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital ( Site 2903)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 2904)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 2901)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 2902)
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2003)
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi ( Site 2004)
  • Edirne, Turkey, 22030
    • Trakya Universitesi Tip Fakultesi ( Site 2000)
  • Erzurum, Turkey, 25240
    • Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2005)
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2002)
  • Izmir, Turkey, 35040
    • Ege Universitesi Tip Fakultesi Hastanesi ( Site 2001)
  • Istanbul
    • Sakarya, Istanbul, Turkey, 54290
      • Sakarya Universitesi Tip Fakultesi ( Site 2007)
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust ( Site 2209)
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital ( Site 2200)
  • Dundee City
    • Dundee, Dundee City, United Kingdom, DD1 9SY
      • Ninewells Hospital and Medical School ( Site 2207)
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G12 0YN
      • The Beatson West of Scotland Cancer Centre ( Site 2204)
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2BU
      • University College London Hospitals NHS Foundation Trust ( Site 2201)
    • London, London, City Of, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Foundation Trust ( Site 2202)
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden NHS Trust ( Site 2203)
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV2 2DX
      • University Hospital Coventry and Warwickshire NHS Trust ( Site 2205)
• United States
  • California
    • Los Angeles, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica ( Site 0003)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center ( Site 0009)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center ( Site 0017)
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University ( Site 0052)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Center ( Site 0019)
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Medical Center ( Site 0020)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System ( Site 0023)
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan ( Site 0025)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 0027)
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital ( Site 0051)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center ( Site 0032)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • AHN West Penn Hospital-AHN Esophageal and Lung Institute ( Site 0058)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma
• Is not expected to require tumor resection during the treatment course
• Has gastroesophageal adenocarcinoma that is not HER-2/neu positive
• Has measurable disease as defined by RECIST 1.1 by scan with IV contrast as determined by the local site investigator
• Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for ≥7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy-whichever comes last
• Female participants not pregnant or breastfeeding are eligible to participate if not a women of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle, and do not donate eggs (ova, oocytes) to others or freeze/store for their own use, and abstain from breastfeeding during the intervention period through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy-whichever occurs last
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function

Exclusion Criteria:

• Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ) esophageal adenocarcinoma
• Has had major surgery within 28 days prior to first dose of study interventions
• Has had radiotherapy within 14 days of randomization
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
• Has known CNS metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to treatment with an monoclonal antibody (mAb) or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products
• Has had an allogeneic tissue/solid organ transplant
• Has perforation risks or significant gastrointestinal (GI) bleeding
• Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Has received prior therapy with anti- vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
• Has inadequate cardiac function
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has poorly controlled diarrhea
• Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment.
• Has peripheral neuropathy ≥Grade 2
• Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
• Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
• Has weight loss of >20% within the last 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib + Pembrolizumab + Chemotherapy; Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days).	Biological: Pembrolizumab; 400 mg Q6W by IV infusion; Other Names: MK-3475; Keytruda®; Biological: Lenvatinib; Administered PO QD, 8 mg induction/20 mg consolidation.; Other Names: E7080; MK-7902; Drug: Oxaliplatin; 130 mg/m^2 administered by IV infusion on Day 1 of Weeks 1 and 4 of each Q6W cycle as part of CAPOX chemotherapy, or 85 mg/m^2 administered by IV infusion on Day 1 and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.; Drug: Capecitabine; 1000 mg/m^2 administered PO twice daily (BID) on Days 1-14, 22-35 of each Q6W cycle as part of CAPOX chemotherapy.; Drug: Leucovorin (or Levoleucovorin); Administered by IV infusion at 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) on Day 1, and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.; Drug: 5-FU; 400 mg/m^2 bolus IV infusion followed by 2400 mg/m^2 continuous IV infusion administered on Day 1, and Week 1, 3, 5, of each Q2W cycle as part of mFOLFOX6 chemotherapy.
Experimental: Chemotherapy; Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days).	Drug: Oxaliplatin; 130 mg/m^2 administered by IV infusion on Day 1 of Weeks 1 and 4 of each Q6W cycle as part of CAPOX chemotherapy, or 85 mg/m^2 administered by IV infusion on Day 1 and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.; Drug: Capecitabine; 1000 mg/m^2 administered PO twice daily (BID) on Days 1-14, 22-35 of each Q6W cycle as part of CAPOX chemotherapy.; Drug: Leucovorin (or Levoleucovorin); Administered by IV infusion at 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) on Day 1, and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.; Drug: 5-FU; 400 mg/m^2 bolus IV infusion followed by 2400 mg/m^2 continuous IV infusion administered on Day 1, and Week 1, 3, 5, of each Q2W cycle as part of mFOLFOX6 chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)	Hematologic DLTs were 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 included 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, or any grade thromboembolic event. The number of participants in Part 1 with DLTs will be reported by treatment arm.	Up to ~21 days
Part 1: Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 1 with AEs will be reported by treatment arm.	Up to ~28 months
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 1 that discontinued study due to an AE will be reported by treatment arm.	Up to ~25 months
Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1	OS is defined as the time from randomization to death due to any cause. OS will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.	Up to ~41 months
Part 2: OS in All Participants	OS is defined as the time from randomization to death due to any cause. OS will be reported by treatment arm for all participants in Part 2.	Up to ~41 months
Part 2: 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 Participants with PD-L1 CPS ≥1	PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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. PFS will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.	Up to ~31 months
Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants	PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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. PFS will be reported by treatment arm for all participants in Part 2.	Up to ~31 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Number of Participants with AEs	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 2 with AEs will be reported by treatment arm.	Up to ~28 months
Part 2: Number of Participants who Discontinued Study Treatment Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 2 that discontinued study due to an AE will be reported by treatment arm.	Up to ~25 months
Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and assessed by BICR. ORR will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.	Up to ~31 months
Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants	ORR is defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and assessed by BICR. ORR will be reported by treatment arm for all participants in Part 2.	Up to ~31 months
Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1	For participants who demonstrated confirmed CR or PR, DOR is defined as the time from the first CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) to subsequent PD or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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. DOR will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.	Up to ~31 months
Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants	For participants who demonstrated confirmed CR or PR, DOR is defined as the time from the first CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) to subsequent PD or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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. DOR will be reported by treatment arm for all participants in Part 2.	Up to ~31 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Estimated): February 2, 2026
• Study Completion (Estimated): February 2, 2026

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Protein Kinase Inhibitors; Vitamins; Immune Checkpoint Inhibitors; Antidotes; Vitamin B Complex; Capecitabine; Oxaliplatin; Pembrolizumab; Leucovorin; Levoleucovorin; Lenvatinib
• Other Study ID Numbers: 7902-015; MK-7902-015 (Other Identifier: Merck); E7080-G000-321 (Other Identifier: Eisai); jRCT2051200127 (Registry Identifier: jRCT); 2020-001990-53 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

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