Advanced/Metastatic Gastroesophageal AdenocarcinomaPhase 3NCT04662710
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)
A Phase 3 study testing Pembrolizumab, Lenvatinib and Oxaliplatin in people with Advanced/Metastatic Gastroesophageal Adenocarcinoma, run by Merck Sharp & Dohme LLC at 177 sites in 24 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/Metastatic Gastroesophageal Adenocarcinoma
- What is being tested?
- Pembrolizumab, Lenvatinib and Oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 895 participants
- Where
- 177 sitesin 24 countries
- Study dates
- 30 Dec 2020to 30 Mar 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 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 human epidermal growth factor receptor 2 (HER-2)/neu positive
- Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (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
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- 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
Who cannot join
- 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 central nervous system (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
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- 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-programmed cell death 1 (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 ribonucleic acid (RNA) [qualitative] is detected) infection
- Has weight loss of >20% within the last 3 months
Trial locations and contacts
177 sites in 24 countries.
177 sites in 24 countries
China28 sites
Cancer Hospital Chinese Academy of Medical Sciences ( Site 2403)
Beijing, Beijing Municipality, 100021
Beijing Cancer Hospital ( Site 2453)
Beijing, Beijing Municipality, 100035
Jilin Cancer Hospital ( Site 2438)
Changchun, Jilin, 130012
Hunan Cancer Hospital ( Site 2440)
Changsha, Hunan, 410006
Changzhou Cancer Hospital-Department of Oncology ( Site 2458)
Changzhou, Jiangsu, 213000
Fujian Provincial Cancer Hospital ( Site 2408)
Fuzhou, Fujian, 350014
The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si
Fuzhou, Fujian, 350025
Nanfang Hospital ( Site 2456)
Guangzhou, Guangdong, 510000
The Affiliated Hospital Of Hainan Medical University-Cancer rehabilitation and palliative treatment
Haikou, Hainan, 570102
The First Affiliated Hospital of Zhejiang University ( Site 2414)
Hangzhou, Zhejiang, 310009
Sir Run Run Shaw Hospital ( Site 2412)
Hangzhou, Zhejiang, 310016
Harbin Medical University Cancer Hospital ( Site 2410)
Harbin, Heilongjiang, 150081
Anhui Provincial Hospital ( Site 2415)
Hefei, Anhui, 230001
First Hospital of Lanzhou University ( Site 2417)
Lanzhou, Gansu, 730000
LinYi Cancer Hospital-Gastrology department ( Site 2463)
Linyi, Shandong, 276000
Nanjing Drum Tower Hospital ( Site 2419)
Nanjing, Jiangsu, 210008
Nantong Tumor Hospital-Digestive Oncology ( Site 2464)
Nantong, Jiangsu, 226361
Shanghai General Hospital ( Site 2424)
Shanghai, Shanghai Municipality, 200080
Shanghai East Hospital ( Site 2455)
Shanghai, Shanghai Municipality, 200120
Fourth Hospital Of Hebei Medical University ( Site 2441)
Shijiazhuang, Hebei, 050011
Tianjin Medical University Cancer Institute & Hospital ( Site 2447)
Tianjin, Tianjin Municipality, 300060
Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2428)
Ürümqi, Xinjiang, 830011
Hubei Cancer Hospital ( Site 2429)
Wuhan, Hubei, 430079
Tang Du Hospital ( Site 2432)
Xi'an, Shaanxi, 710038
The First Affiliated Hospital of Xiamen University ( Site 2420)
Xiamen, Fujian, 361003
The First Affiliated Hospital of Xiamen University ( Site 2446)
Xiamen, Fujian, 361003
Zhongshan Hospital Affiliated to Xiamen University ( Site 2421)
Xiamen, Fujian, 361004
Henan Cancer Hospital ( Site 2443)
Zhengzhou, Henan, 450008
Japan16 sites
Hyogo Cancer Center ( Site 2621)
Akashi, Hyōgo, 673-8558
National Hospital Organization Kyushu Cancer Center ( Site 2609)
Fukuoka, 811-1395
Kansai Medical University Hospital ( Site 2622)
Hirakata, Osaka, 573-1191
Hiroshima City Hiroshima Citizens Hospital ( Site 2612)
Hiroshima, 730-8518
Ibaraki Prefectural Central Hospital ( Site 2618)
Kasama, Ibaraki, 309-1793
National Cancer Center Hospital East ( Site 2601)
Kashiwa, Chiba, 277-8577
Kagawa University Hospital ( Site 2611)
Kita-gun, Kagawa-ken, 761-0793
Saitama Cancer Center ( Site 2604)
Kitaadachi-gun, Saitama, 362-0806
Kobe City Medical Center General Hospital ( Site 2606)
Kobe, Hyōgo, 650-0047
National Hospital Organization Shikoku Cancer Center ( Site 2610)
Matsuyama, Ehime, 791-0280
Aichi Cancer Center Hospital ( Site 2603)
Nagoya, Aichi-ken, 464-8681
Osaka International Cancer Institute ( Site 2607)
Osaka, 5418567
Kindai University Hospital ( Site 2600)
Sayama, Osaka, 5898511
National Cancer Center Hospital ( Site 2602)
Tokyo, 104-0045
The Cancer Institute Hospital of JFCR ( Site 2605)
Tokyo, 135-8550
Kanagawa Cancer Center ( Site 2608)
Yokohama, Kanagawa, 241-8515
United States12 sites
Johns Hopkins University ( Site 0052)
Baltimore, Maryland, 21224
Dana Farber Cancer Center ( Site 0019)
Boston, Massachusetts, 02215
Henry Ford Health System ( Site 0023)
Detroit, Michigan, 48202
Cancer and Hematology Centers of Western Michigan ( Site 0025)
Grand Rapids, Michigan, 49503
UCLA Hematology/Oncology - Santa Monica ( Site 0003)
Los Angeles, California, 90404
James Graham Brown Cancer Center ( Site 0017)
Louisville, Kentucky, 40202
Mount Sinai Hospital ( Site 0051)
New York, New York, 10029
Memorial Sloan Kettering Cancer Center ( Site 0032)
New York, New York, 10065
AHN West Penn Hospital-AHN Esophageal and Lung Institute ( Site 0058)
Pittsburgh, Pennsylvania, 15224
Washington University School of Medicine ( Site 0027)
St Louis, Missouri, 63110
Georgetown University Medical Center ( Site 0009)
Washington D.C., District of Columbia, 20007
UMASS Memorial Medical Center ( Site 0020)
Worcester, Massachusetts, 01655
France10 sites
Institut du Cancer Avignon-Provence ( Site 1103)
Avignon, Vaucluse, 84918
Centre Francois Baclesse ( Site 1107)
Caen, Calvados, 14076
Hopital Henri Mondor ( Site 1105)
Créteil, Val-de-Marne, 94010
Centre Georges Francois Leclerc ( Site 1106)
Dijon, Cote-d Or, 21079
Centre Hospitalier Annecy Genevois ( Site 1117)
Epagny Metz-Tessy, Haute-Savoie, 74370
Hôpital Edouard Herriot ( Site 1116)
Lyon, Auvergne-Rhône-Alpes, 69003
CHU Hotel Dieu Nantes ( Site 1101)
Nantes, Pays de la Loire Region, 44093
Hopital Saint Louis ( Site 1100)
Paris, 75010
CHU Hopital Saint Antoine ( Site 1102)
Paris, 75012
CHU Bordeaux Haut-Leveque ( Site 1110)
Pessac, Gironde, 33604
Russia9 sites
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1816)
Chelyabinsk, Chelyabinsk Oblast, 454087
National Medical and Surgical Center n.a.N.I.Pirogov ( Site 1805)
Moscow, Moscow, 105203
Blokhin National Medical Oncology ( Site 1800)
Moscow, Moscow, 115478
Central Clinical Hospital with Polyclinic ( Site 1801)
Moscow, Moscow, 121359
Leningrad Regional Oncology Center ( Site 1810)
Saint Petersburg, Sankt-Peterburg, 188663
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1809)
Saint Petersburg, Sankt-Peterburg, 197758
St Petersburg City Clinical Oncology Dispensary ( Site 1808)
Saint Petersburg, Sankt-Peterburg, 198255
Medical University REAVIZ ( Site 1814)
Samara, Samara Oblast, 443011
Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1821)
Yaroslavl, Yaroslavl Oblast, 150054
South Korea9 sites
Hallym University Sacred Heart Hospital ( Site 2806)
Anyang-si, Kyonggi-do, 14068
Konyang University ( Site 2807)
Daejeon, Taejon-Kwangyokshi, 35365
Seoul National University Bundang Hospital ( Site 2804)
Seongnam-si, Kyonggi-do, 13620
Seoul National University Hospital ( Site 2803)
Seoul, 03080
Severance Hospital Yonsei University Health System ( Site 2800)
Seoul, 03722
Gangnam Severance Hospital ( Site 2805)
Seoul, 06273
Samsung Medical Center ( Site 2801)
Seoul, 06351
Korea University Guro Hospital ( Site 2808)
Seoul, 08308
Asan Medical Center ( Site 2802)
Songpagu, Seoul, 05505
Italy8 sites
Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1611)
Catanzaro, 88100
Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1608)
Meldola, Abruzzo, 47014
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1610)
Milan, Lombardy, 20133
IRCCS Ospedale San Raffaele di Milano ( Site 1603)
Milan, 20132
A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1604)
Naples, 80131
Humanitas Research Hospital ( Site 1600)
Rozzano, Lombardy, 20089
Presidio Ospedaliero Universitario Santa Maria della Misericordia ( Site 1609)
Udine, Friuli Venezia Giulia, 33100
AULSS8 Berica-Ospedale S.Bortolo ( Site 1607)
Vicenza, Veneto, 36100
United Kingdom8 sites
Addenbrooke's Hospital ( Site 2200)
Cambridge, Cambridgeshire, CB2 0QQ
University Hospital Coventry and Warwickshire NHS Trust ( Site 2205)
Coventry, Warwickshire, CV2 2DX
Ninewells Hospital and Medical School ( Site 2207)
Dundee, Dundee City, DD1 9SY
The Beatson West of Scotland Cancer Centre ( Site 2204)
Glasgow, Glasgow City, G12 0YN
University College London Hospitals NHS Foundation Trust ( Site 2201)
London, London, City of, NW1 2BU
Royal Marsden NHS Foundation Trust ( Site 2202)
London, London, City of, SW3 6JJ
The Christie NHS Foundation Trust ( Site 2209)
Manchester, M20 4BX
Royal Marsden NHS Trust ( Site 2203)
Sutton, Surrey, SM2 5PT
Argentina7 sites
Fundacion Favaloro ( Site 0201)
Buenos Aires, C1093AAS
Hospital Aleman ( Site 0210)
Buenos Aires, C1118AAT
Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0207)
Buenos Aires, C1264AAA
CEMIC ( Site 0209)
Buenos Aires, C1431FWO
IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)
Caba, Buenos Aires, C1012AAR
Instituto Medico Alexander Fleming ( Site 0208)
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1426ANZ
Hospital Privado de Cordoba ( Site 0204)
Córdoba, X5016KEH
Germany7 sites
Charite Berlin Campus Virchow-Klinikum ( Site 1202)
Berlin, 13353
Krankenhaus Nordwest ( Site 1205)
Frankfurt am Main, Hesse, 60488
Facharztzentrum Eppendorf ( Site 1201)
Hamburg, 20249
Medizinische Hochschule Hannover ( Site 1210)
Hanover, Lower Saxony, 30625
Universitaetsklinikum Leipzig ( Site 1211)
Leipzig, Saxony, 04103
Klinikum Rechts der Isar der TU Muenchen ( Site 1200)
Muechen, Bavaria, 81675
Universitaetsklinikum Regensburg ( Site 1203)
Regensburg, Bavaria, 93053
Israel7 sites
Soroka Medical Center ( Site 1507)
Beersheba, 8410101
Hillel Yaffe Medical Center ( Site 1503)
Hadera, 3810004
Rambam Health Care Campus-Oncology Division ( Site 1502)
Haifa, 3109601
Hadassah Ein Kerem Medical Center ( Site 1501)
Jerusalem, 9112001
Meir Medical Center ( Site 1504)
Kfar Saba, 4428164
Rabin Medical Center ( Site 1506)
Petah Tikva, 4941492
Sourasky Medical Center ( Site 1500)
Tel Aviv, 6423906
Turkey (Türkiye)7 sites
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2003)
Ankara, 06100
Memorial Ankara Hastanesi ( Site 2004)
Ankara, 06520
Trakya Universitesi Tip Fakultesi ( Site 2000)
Edirne, 22030
Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2005)
Erzurum, 25240
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2002)
Istanbul, 34098
Ege Universitesi Tip Fakultesi Hastanesi ( Site 2001)
Izmir, 35040
Sakarya Universitesi Tip Fakultesi ( Site 2007)
Sakarya, Istanbul, 54290
Chile6 sites
IC La Serena Research ( Site 0410)
La Serena, Coquimbo Region, 1720430
Fundacion Arturo Lopez Perez FALP ( Site 0403)
Santiago, Region M. de Santiago, 7500836
Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)
Santiago, Region M. de Santiago, 7550000
Bradfordhill ( Site 0404)
Santiago, Region M. de Santiago, 8420383
Clinica Universidad Catolica del Maule ( Site 0411)
Talca, Maule Region, 3460000
Centro Investigación del Cáncer James Lind ( Site 0414)
Temuco, Araucania, Temuco
Colombia6 sites
Clinica de la Costa S.A.S. ( Site 0502)
Barranquilla, Atlántico, 080020
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0501)
Bogotá, Bogota D.C., 111321
Oncomedica S.A. ( Site 0507)
Montería, Departamento de Córdoba, 230002
Instituto Cancerologico de Narino Ltda ( Site 0504)
Pasto, Departamento de Nariño, 520001
Oncologos del Occidente S.A. ( Site 0525)
Pereira, Risaralda Department, 660001
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0508)
Valledupar, Cesar Department, 200001
Guatemala6 sites
Clinica Privada Dr Rixci Ramirez Fallas ( Site 0702)
Guatemala City, 01010
Oncologika S.A. ( Site 0704)
Guatemala City, 01010
Oncomedica ( Site 0701)
Guatemala City, 01010
Soluciones Gastrointestinales S.A. ( Site 0706)
Guatemala City, 01010
Sanatorio Nuestra Senora del Pilar ( Site 0705)
Guatemala City, 01015
Medi-K Cayala ( Site 0700)
Guatemala City, 01016
Poland5 sites
Przychodnia Lekarska KOMED ( Site 1701)
Konin, Greater Poland Voivodeship, 62-500
Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 1703)
Poznan, Greater Poland Voivodeship, 60-780
Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1702)
Przemyśl, Podkarpackie Voivodeship, 37-700
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1704)
Warsaw, Masovian Voivodeship, 02-034
Dolnoslaskie Centrum Onkologii. ( Site 1712)
Wroclaw, Lower Silesian Voivodeship, 53-413
Australia4 sites
Royal Brisbane and Women s Hospital ( Site 2304)
Herston, Queensland, 4029
Nepean Hospital ( Site 2305)
Kingswood, New South Wales, 2747
Hollywood Private Hospital-Medical Oncology ( Site 2308)
Nedlands, Western Australia, 6009
Wollongong Hospital ( Site 2307)
Wollongong, New South Wales, 2500
Belgium4 sites
UZ Gent ( Site 1002)
Ghent, Oost-Vlaanderen, 9000
UZ Leuven ( Site 1004)
Leuven, Vlaams-Brabant, 3000
AZ Delta ( Site 1006)
Roeselare, West-Vlaanderen, 8800
CHU UCL Namur Site de Godinne ( Site 1005)
Yvoir, Namur, 5530
Spain4 sites
Hospital General Universitari Vall d Hebron ( Site 1907)
Barcelona, 08035
Hospital General Gregorio Maranon de Madrid ( Site 1904)
Madrid, 28007
Hospital Universitario General de Asturias ( Site 1901)
Oviedo, Principality of Asturias, 33011
Hospital Universitario Marques de Valdecilla ( Site 1902)
Santander, Cantabria, 39008
Taiwan4 sites
China Medical University Hospital ( Site 2903)
Taichung, 40447
National Cheng Kung University Hospital ( Site 2904)
Tainan, 704
National Taiwan University Hospital ( Site 2901)
Taipei, 10048
Chang Gung Medical Foundation. Linkou ( Site 2902)
Taoyuan, 333
Canada3 sites
Queen Elizabeth II Health Sciences Centre ( Site 0101)
Halifax, Nova Scotia, B3H 2Y9
Hamilton Health Sciences - Juravinski Site ( Site 0106)
Hamilton, Ontario, L8V 5C2
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103)
Sherbrooke, Quebec, J1H 5N4
Hong Kong3 sites
Prince of Wales Hospital ( Site 2503)
Hong Kong
Princess Margaret Hospital. ( Site 2502)
Hong Kong
Queen Mary Hospital ( Site 2501)
Hong Kong
Costa Rica2 sites
CIMCA-Hemato-Oncology ( Site 0601)
San José, Provincia de San José, 10103
Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0602)
Santa Ana, Provincia de San José, 10903
Ireland2 sites
St James Hospital ( Site 1400)
Dublin, Leinster, Dublin 8
Beaumont Hospital ( Site 1402)
Dublin, Dublin 9
About this study
Official title: 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.
Read the 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.
As of Amendment 8 (Effective 06/10/2025), Second Course will no longer be offered. Any participant currently receiving Second Course retreatment will be able to continue treatment as planned. Imaging will be performed per local standard of care.
- Being tested
- Pembrolizumab, Lenvatinib, Oxaliplatin, Capecitabine, Leucovorin (or Levoleucovorin)
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Medical subject headings
- 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 Q6W by IV infusion
LenvatinibBiological
Also called MK-7902, E7080
Administered PO QD, 8 mg induction/20 mg consolidation.
OxaliplatinDrug
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.
CapecitabineDrug
1000 mg/m^2 administered PO twice daily (BID) on Days 1-14, 22-35 of each Q6W cycle as part of CAPOX chemotherapy.
Leucovorin (or Levoleucovorin)Drug
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.
5-FUDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib + Pembrolizumab + Chemotherapy | Experimental | 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). Receives: Biological: Pembrolizumab; Biological: Lenvatinib; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Leucovorin (or Levoleucovorin); Drug: 5-FU |
| Chemotherapy | Experimental | Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days). Receives: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Leucovorin (or Levoleucovorin); Drug: 5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as a specific adverse event graded for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Hematologic DLTs included 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. Nonhematologic DLTs 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, any grade thromboembolic event, or any Grade 3 nonhematologic laboratory value if medical intervention was required or the abnormality led to hospitalization. The number of participants in Part 1 with DLTs is reported.
Measured: 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 is reported
Measured: Up to ~44 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 treatment due to an AE is reported.
Measured: Up to ~29 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 is reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Measured: 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 is reported by treatment arm for all participants in Part 2.
Measured: 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 is reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Measured: Up to ~29 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 is reported by treatment arm for all participants in Part 2.
Measured: Up to ~29 months
Secondary outcomes (6)
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 is reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Measured: Up to ~29 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 is reported by treatment arm for all participants in Part 2.
Measured: Up to ~29 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 is reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Measured: Up to ~41 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 is reported by treatment arm for all participants in Part 2.
Measured: Up to ~41 months
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 is reported by treatment arm.
Measured: Up to ~41 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 treatment due to an AE is reported by treatment arm.
Measured: Up to ~41 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start30 Dec 2020
- Primary completion29 Oct 2024
- Study completion30 Mar 2026
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 Advanced/Metastatic Gastroesophageal AdenocarcinomaStudies 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
- 895 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
- NCT04662710
- Sponsor's protocol ID
- 7902-015
- Other IDs
- MK-7902-015, E7080-G000-321, 2051200127, 2023-504834-23-00, U1111-1288-1010, 2020-001990-53, 2023
- Status last verified
- Apr 2026
- First submitted
- 4 Dec 2020
- Last updated
- 28 Apr 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
Shitara K, Lorenzen S, Li J, Bai Y, Fernandez MG, Aguilar M, Shoji H, Reyes-Cosmelli F, Pena YR, Corrales L, Wyrwicz L, Eyzaguirre DA, Pan Y, Ryu MH, Cohen DJ, Wainberg ZA, Ku G, Tabernero J, Van Cutsem E, Qin SK, Oh DY, Xu J, Liang LW, Bordia S, Bhagia P, Rha SY; LEAP-015 Investigators. Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study. J Clin Oncol. 2025 Aug;43(22):2502-2514. doi: 10.1200/JCO-25-00748. Epub 2025 May 31.
PubMed 40448579