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)
Advanced/Metastatic Gastroesophageal Adenocarcinoma

About this trial
This is an interventional treatment trial for Advanced/Metastatic Gastroesophageal Adenocarcinoma focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
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
Sites / Locations
- UCLA Hematology/Oncology - Santa Monica ( Site 0003)
- Georgetown University Medical Center ( Site 0009)
- James Graham Brown Cancer Center ( Site 0017)
- Johns Hopkins University ( Site 0052)
- Dana Farber Cancer Center ( Site 0019)
- UMASS Memorial Medical Center ( Site 0020)
- Henry Ford Health System ( Site 0023)
- Cancer and Hematology Centers of Western Michigan ( Site 0025)
- Washington University School of Medicine ( Site 0027)
- Mount Sinai Hospital ( Site 0051)
- Memorial Sloan Kettering Cancer Center ( Site 0032)
- AHN West Penn Hospital-AHN Esophageal and Lung Institute ( Site 0058)
- IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)
- Instituto Medico Alexander Fleming ( Site 0208)
- Fundacion Favaloro ( Site 0201)
- Hospital Aleman ( Site 0210)
- Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0207)
- CEMIC ( Site 0209)
- Hospital Privado de Cordoba ( Site 0204)
- Nepean Hospital ( Site 2305)
- Wollongong Hospital ( Site 2307)
- Royal Brisbane and Women s Hospital ( Site 2304)
- Hollywood Private Hospital-Medical Oncology ( Site 2308)
- CHU UCL Namur Site de Godinne ( Site 1005)
- UZ Gent ( Site 1002)
- UZ Leuven ( Site 1004)
- AZ Delta ( Site 1006)
- Queen Elizabeth II Health Sciences Centre ( Site 0101)
- Hamilton Health Sciences - Juravinski Site ( Site 0106)
- CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103)
- Centro Investigación del Cáncer James Lind ( Site 0414)
- IC La Serena Research ( Site 0410)
- Clinica Universidad Catolica del Maule ( Site 0411)
- Fundacion Arturo Lopez Perez FALP ( Site 0403)
- Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)
- Bradfordhill ( Site 0404)
- Anhui Provincial Hospital ( Site 2415)
- Cancer Hospital Chinese Academy of Medical Sciences ( Site 2403)
- Beijing Cancer Hospital ( Site 2453)
- Fujian Provincial Cancer Hospital ( Site 2408)
- The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si
- The First Affiliated Hospital of Xiamen University ( Site 2420)
- The First Affiliated Hospital of Xiamen University ( Site 2446)
- Zhongshan Hospital Affiliated to Xiamen University ( Site 2421)
- First Hospital of Lanzhou University ( Site 2417)
- Nanfang Hospital ( Site 2456)
- The Affiliated Hospital Of Hainan Medical University-Cancer rehabilitation and palliative treatment
- Fourth Hospital Of Hebei Medical University ( Site 2441)
- Harbin Medical University Cancer Hospital ( Site 2410)
- Henan Cancer Hospital ( Site 2443)
- Hubei Cancer Hospital ( Site 2429)
- Hunan Cancer Hospital ( Site 2440)
- Changzhou Cancer Hospital-Department of Oncology ( Site 2458)
- Nanjing Drum Tower Hospital ( Site 2419)
- Nantong Tumor Hospital-Digestive Oncology ( Site 2464)
- Jilin Cancer Hospital ( Site 2438)
- Tang Du Hospital ( Site 2432)
- LinYi Cancer Hospital-Gastrology department ( Site 2463)
- Shanghai General Hospital ( Site 2424)
- Shanghai East Hospital ( Site 2455)
- Tianjin Medical University Cancer Institute & Hospital ( Site 2447)
- Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2428)
- The First Affiliated Hospital of Zhejiang University ( Site 2414)
- Sir Run Run Shaw Hospital ( Site 2412)
- Clinica de la Costa S.A.S. ( Site 0502)
- Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0508)
- Oncomedica S.A. ( Site 0507)
- Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0501)
- Instituto Cancerologico de Narino Ltda ( Site 0504)
- Oncologos del Occidente S.A. ( Site 0525)
- CIMCA-Hemato-Oncology ( Site 0601)
- Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0602)
- Centre Francois Baclesse ( Site 1107)
- Centre Georges Francois Leclerc ( Site 1106)
- CHU Bordeaux Haut-Leveque ( Site 1110)
- Centre Hospitalier Annecy Genevois ( Site 1117)
- CHU Hotel Dieu Nantes ( Site 1101)
- Hôpital Edouard Herriot ( Site 1116)
- Hopital Henri Mondor ( Site 1105)
- Institut du Cancer Avignon-Provence ( Site 1103)
- Hopital Saint Louis ( Site 1100)
- CHU Hopital Saint Antoine ( Site 1102)
- Klinikum Rechts der Isar der TU Muenchen ( Site 1200)
- Universitaetsklinikum Regensburg ( Site 1203)
- Krankenhaus Nordwest ( Site 1205)
- Medizinische Hochschule Hannover ( Site 1210)
- Universitaetsklinikum Leipzig ( Site 1211)
- Charite Berlin Campus Virchow-Klinikum ( Site 1202)
- Facharztzentrum Eppendorf ( Site 1201)
- Clinica Privada Dr Rixci Ramirez Fallas ( Site 0702)
- Oncologika S.A. ( Site 0704)
- Oncomedica ( Site 0701)
- Soluciones Gastrointestinales S.A. ( Site 0706)
- Sanatorio Nuestra Senora del Pilar ( Site 0705)
- Medi-K Cayala ( Site 0700)
- Prince of Wales Hospital ( Site 2503)
- Princess Margaret Hospital. ( Site 2502)
- Queen Mary Hospital ( Site 2501)
- St James Hospital ( Site 1400)
- Beaumont Hospital ( Site 1402)
- Soroka Medical Center ( Site 1507)
- Hillel Yaffe Medical Center ( Site 1503)
- Rambam Health Care Campus-Oncology Division ( Site 1502)
- Hadassah Ein Kerem Medical Center ( Site 1501)
- Meir Medical Center ( Site 1504)
- Rabin Medical Center ( Site 1506)
- Sourasky Medical Center ( Site 1500)
- Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1608)
- Presidio Ospedaliero Universitario Santa Maria della Misericordia ( Site 1609)
- Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1610)
- Humanitas Research Hospital ( Site 1600)
- AULSS8 Berica-Ospedale S.Bortolo ( Site 1607)
- Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1611)
- IRCCS Ospedale San Raffaele di Milano ( Site 1603)
- A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1604)
- Aichi Cancer Center Hospital ( Site 2603)
- National Cancer Center Hospital East ( Site 2601)
- National Hospital Organization Shikoku Cancer Center ( Site 2610)
- Hyogo Cancer Center ( Site 2621)
- Kobe City Medical Center General Hospital ( Site 2606)
- Ibaraki Prefectural Central Hospital ( Site 2618)
- Kagawa University Hospital ( Site 2611)
- Kanagawa Cancer Center ( Site 2608)
- Kansai Medical University Hospital ( Site 2622)
- Kindai University Hospital ( Site 2600)
- Saitama Cancer Center ( Site 2604)
- National Hospital Organization Kyushu Cancer Center ( Site 2609)
- Hiroshima City Hiroshima Citizens Hospital ( Site 2612)
- Osaka International Cancer Institute ( Site 2607)
- National Cancer Center Hospital ( Site 2602)
- The Cancer Institute Hospital of JFCR ( Site 2605)
- Hallym University Sacred Heart Hospital ( Site 2806)
- Seoul National University Bundang Hospital ( Site 2804)
- Asan Medical Center ( Site 2802)
- Konyang University ( Site 2807)
- Seoul National University Hospital ( Site 2803)
- Severance Hospital Yonsei University Health System ( Site 2800)
- Gangnam Severance Hospital ( Site 2805)
- Samsung Medical Center ( Site 2801)
- Korea University Guro Hospital ( Site 2808)
- Dolnoslaskie Centrum Onkologii. ( Site 1712)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1704)
- Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1702)
- Przychodnia Lekarska KOMED ( Site 1701)
- Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 1703)
- Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1816)
- National Medical and Surgical Center n.a.N.I.Pirogov ( Site 1805)
- Blokhin National Medical Oncology ( Site 1800)
- Central Clinical Hospital with Polyclinic ( Site 1801)
- Medical University REAVIZ ( Site 1814)
- St Petersburg City Clinical Oncology Dispensary ( Site 1808)
- Leningrad Regional Oncology Center ( Site 1810)
- Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1809)
- Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1821)
- Hospital Universitario General de Asturias ( Site 1901)
- Hospital Universitario Marques de Valdecilla ( Site 1902)
- Hospital General Universitari Vall d Hebron ( Site 1907)
- Hospital General Gregorio Maranon de Madrid ( Site 1904)
- China Medical University Hospital ( Site 2903)
- National Cheng Kung University Hospital ( Site 2904)
- National Taiwan University Hospital ( Site 2901)
- Chang Gung Medical Foundation. Linkou ( Site 2902)
- Sakarya Universitesi Tip Fakultesi ( Site 2007)
- Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2003)
- Memorial Ankara Hastanesi ( Site 2004)
- Trakya Universitesi Tip Fakultesi ( Site 2000)
- Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2005)
- Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2002)
- Ege Universitesi Tip Fakultesi Hastanesi ( Site 2001)
- Addenbrooke's Hospital ( Site 2200)
- Ninewells Hospital and Medical School ( Site 2207)
- The Beatson West of Scotland Cancer Centre ( Site 2204)
- University College London Hospitals NHS Foundation Trust ( Site 2201)
- Royal Marsden NHS Foundation Trust ( Site 2202)
- Royal Marsden NHS Trust ( Site 2203)
- University Hospital Coventry and Warwickshire NHS Trust ( Site 2205)
- The Christie NHS Foundation Trust ( Site 2209)
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Lenvatinib + Pembrolizumab + Chemotherapy
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).
Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days).