Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)

A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)

The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).

Study Overview

• Status: Completed
• Conditions: Gastric Neoplasms; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Cisplatin; Drug: 5-FU; Drug: Oxaliplatin; Drug: Capecitabine; Drug: S-1; Biological: Trastuzumab; Biological: Placebo

Detailed Description

Pembrolizumab (200 mg) or placebo will be administered intravenously [IV] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will either be FP (80 mg/m^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800 mg/m^2 5-fluorouracil [5-FU] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000 mg/m^2 capecitabine administered orally twice daily [BID] on days 1-14 of each 3-week cycle and 130 mg/m^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine [CDHP], and potassium oxonate [Oxo]) administered orally BID according to Body Surface Area (BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m^2) administered IV on Day 1 each 3-week cycle.

• Study Type: Interventional
• Enrollment (Actual): 738
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital ( Site 2206)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital ( Site 2200)
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre ( Site 2207)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health ( Site 2202)
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0201)
  • São Paulo, Brazil, 03102-002
    • IBCC - Instituto Brasileiro de Controle do Cancer ( Site 0204)
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-230
      • Instituto do Cancer do Ceara ( Site 0208)
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Hospital Sao Rafael ( Site 0209)
  • Paraná
    • Curitiba, Paraná, Brazil, 80810-050
      • CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0205)
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700 000
      • Hospital de Caridade de Ijui ( Site 0202)
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao ( Site 0203)
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88034-000
      • CEPON - Centro de Pesquisas Oncologicas ( Site 0200)
• Chile
  • Maule Region
    • Talca, Maule Region, Chile, 3460000
      • Clinica Universidad Catolica del Maule ( Site 0305)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez FALP ( Site 0302)
    • Santiago, Region M. de Santiago, Chile, 7620002
      • Pontificia Universidad Catolica de Chile ( Site 0301)
    • Santiago, Region M. de Santiago, Chile, 8380455
      • Instituto Nacional del Cancer ( Site 0303)
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4780000
      • Centro Investigación del Cáncer James Lind ( Site 0300)
• China
  • Anhui
    • Shanghai, Anhui, China, 200080
      • Shanghai General Hospital ( Site 2404)
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100032
      • Peking Union Medical College Hospital ( Site 2419)
    • Beijing, Beijing Municipality, China, 100071
      • Fifth Medical Center of CPLA General Hospital ( Site 2415)
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital ( Site 2413)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital ( Site 2418)
    • Fuzhou, Fujian, China, 350025
      • 900 Hospital of the Joint ( Site 2420)
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University ( Site 2431)
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital ( Site 2433)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital ( Site 2407)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 2400)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central-South University ( Site 2426)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Cancer Hospital ( Site 2432)
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital Of Jilin University ( Site 2402)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 2424)
    • Shanghai, Shanghai Municipality, China, 200032
      • Zhongshan Hospital affiliated to Fudan University ( Site 2401)
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830001
      • Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2430)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital.Zhejiang University ( Site 2408)
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital ( Site 2412)
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 2409)
• France
  • Paris, France, 75012
    • CHU Hopital Saint Antoine ( Site 0905)
  • Ain
    • Rouen, Ain, France, 76000
      • CHU de Rouen ( Site 0912)
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67098
      • HUS Hopital Hautepierre ( Site 0910)
  • Doubs
    • Besançon, Doubs, France, 25030
      • Hopital Jean Minjoz Besancon ( Site 0901)
  • Finistere
    • Brest, Finistere, France, 29200
      • C.H.R.U. de Brest - Hopital Morvan ( Site 0913)
  • Nord
    • Lille, Nord, France, 59000
      • Centre Oscar Lambret ( Site 0911)
  • Rhone
    • Lyon, Rhone, France, 69008
      • Centre Leon Berard ( Site 0904)
  • Val-de-Marne
    • Saint-Herblain, Val-de-Marne, France, 44805
      • Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0902)
    • Villejuif, Val-de-Marne, France, 94805
      • Institut Gustave Roussy ( Site 0900)
• Germany
  • Berlin, Germany, 13353
    • Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 1026)
  • Bremen, Germany, 28211
    • Klinikum Bremen Nord ( Site 1017)
  • Hamburg, Germany, 20249
    • Facharztzentrum Eppendorf ( Site 1025)
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona ( Site 1000)
  • Baden-Wurttemberg
    • Heilbronn, Baden-Wurttemberg, Germany, 74078
      • SLK-Kliniken Heilbronn ( Site 1015)
    • Ludwigsburg, Baden-Wurttemberg, Germany
      • Klinikum Ludwigsburg ( Site 1014)
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Innere Medizin I, Universitaetsklinikum Tuebingen ( Site 1020)
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Klinikum rechts der Isar der Technischen Universitaet ( Site 1027)
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover ( Site 1019)
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus der Technischen Univ ( Site 1001)
    • Leipzig, Saxony, Germany, 04103
      • Universitaetsklinikum Leipzig AOeR ( Site 1007)
• Guatemala
  • Guatemala City, Guatemala, 01010
    • Celan SA ( Site 0504)
  • Guatemala City, Guatemala, 01010
    • Oncomedica ( Site 0500)
  • Guatemala City, Guatemala, 01015
    • Grupo Angeles SA ( Site 0501)
  • Guatemala City, Guatemala, 01015
    • Nucare Center ( Site 0506)
  • Guatemala City, Guatemala, 01016
    • Medi-K Cayala ( Site 0505)
  • Quetzaltenango, Guatemala, 09001
    • Centro Regional de Sub Especialidades Medicas SA ( Site 0502)
• Ireland
  • Dublin, Ireland, D08NHY1
    • Saint James's Hospital ( Site 1505)
  • Dublin, Ireland, D09 V2N0
    • Beaumont Hospital ( Site 1506)
  • Dublin, Ireland, D24 NR0A
    • Tallaght University Hospital ( Site 1513)
• Israel
  • Beersheba, Israel, 8410101
    • Soroka University Medical Center ( Site 1603)
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus ( Site 1606)
  • Holon, Israel, 5822012
    • Edith Wolfson Medical Center ( Site 1605)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 1604)
  • Kfar Saba, Israel, 4428132
    • Meir Medical Center ( Site 1609)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 1602)
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center. ( Site 1607)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 1601)
• Italy
  • Bergamo, Italy, 24125
    • Humanitas Gavazzeni ( Site 1106)
  • Catanzaro, Italy, 88100
    • Universita Magna Graecia di Catanzaro ( Site 1107)
  • Milan, Italy, 20141
    • IEO Istituto Europeo di Oncologia ( Site 1105)
  • Modena, Italy, 41124
    • Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 1102)
  • Napoli, Italy, 80131
    • A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1103)
  • Padua, Italy, 35128
    • Istituto Oncologico Veneto ( Site 1101)
  • Pescara, Italy, 65100
    • Ospedale Civile Spirito Santo ( Site 1104)
  • Tuscany
    • Pisa, Tuscany, Italy, 56126
      • AUOP Ospedale Santa Chiara ( Site 1100)
• Japan
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center ( Site 2623)
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 2609)
  • Gifu, Japan, 501-1194
    • Gifu University Hospital ( Site 2621)
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital ( Site 2625)
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital ( Site 2601)
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital ( Site 2622)
  • Osaka, Japan, 540-0006
    • National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 26
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 2613)
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center ( Site 2624)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 2612)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 2628)
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Komagome Hospital ( Site 2606)
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR ( Site 2610)
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 2617)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 2605)
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center ( Site 2615)
  • Gunma
    • Ohta, Gunma, Japan, 373-8550
      • Gunma Prefectural Cancer Center ( Site 2602)
  • Hyōgo
    • Akashi, Hyōgo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 2619)
    • Kobe, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital ( Site 2614)
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital ( Site 2611)
  • Kagawa-ken
    • Kita-gun, Kagawa-ken, Japan, 761-0793
      • Kagawa University Hospital ( Site 2604)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 2603)
  • Miyagi
    • Ōsaki, Miyagi, Japan, 989-6183
      • Osaki Citizen Hospital ( Site 2626)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 2618)
    • Sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 2616)
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital ( Site 2600)
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Cancer Center ( Site 2620)
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center Hospital and Research Institute ( Site 2607)
  • Tochigi
    • Utsunomiya, Tochigi, Japan, 320-0834
      • Tochigi Cancer Center ( Site 2627)
  • Tokyo
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital ( Site 2608)
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital ( Site 2300)
• Poland
  • Greater Poland Voivodeship
    • Konin, Greater Poland Voivodeship, Poland, 62-500
      • Przychodnia Lekarska Komed ( Site 1716)
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. J. M. Radeckiego we Wroclawiu ( Site 1705)
    • Wroclaw, Lower Silesian Voivodeship, Poland, 53-413
      • Dolnoslaskie Centrum Onkologii. ( Site 1712)
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-080
      • Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1709)
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-519
      • Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1715)
    • Kościerzyna, Pomeranian Voivodeship, Poland, 83-400
      • Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 1708)
  • Silesian Voivodeship
    • Bielsko-Biala, Silesian Voivodeship, Poland, 43-300
      • Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1710)
• Russia
  • Baskortostan, Respublika
    • Ufa, Baskortostan, Respublika, Russia, 450054
      • Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1807)
  • Chelyabinsk Oblast
    • Chelyabinsk, Chelyabinsk Oblast, Russia, 454087
      • Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1815)
  • Moscow
    • Moscow, Moscow, Russia, 115478
      • Blokhin National Medical Oncology ( Site 1805)
  • Moscow Oblast
    • Podolsk, Moscow Oblast, Russia, 142110
      • Podolsky City Clinical Hospital ( Site 1817)
  • Samara Oblast
    • Samara, Samara Oblast, Russia, 443011
      • Medical University REAVIZ ( Site 1816)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 188663
      • Leningrad Regional Oncology Center ( Site 1800)
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1801)
    • Saint Petersburg, Sankt-Peterburg, Russia, 198255
      • St Petersburg City Clinical Oncology Dispensary ( Site 1812)
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital ( Site 2703)
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System ( Site 2700)
  • Seoul, South Korea, 05505
    • Asan Medical Center ( Site 2702)
  • Seoul, South Korea, 06351
    • Samsung Medical Center ( Site 2701)
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d Hebron ( Site 1401)
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal ( Site 1400)
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche ( Site 1404)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1410)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla ( Site 1405)
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quiron Madrid ( Site 1407)
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias ( Site 1402)
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01370
    • Adana Sehir Hastanesi ( Site 2002)
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2017)
  • Ankara, Turkey (Türkiye), 06200
    • Abdurrahman Yurtaslan Onkoloji Egitim ve Arastirma Hastanesi ( Site 2006)
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Universitesi Tip Fakultesi ( Site 2015)
  • Erzurum, Turkey (Türkiye), 25240
    • Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2000)
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2001)
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylul Universitesi Tip Fakultesi Hastanesi ( Site 2011)
  • Malatya, Turkey (Türkiye), 44280
    • Malatya Inonu Universitesi Tip Fakultesi Hastanesi ( Site 2009)
  • Sakarya, Turkey (Türkiye), 54290
    • Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 2012)
• Ukraine
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Oncology Centre ( Site 2110)
  • Dnipropetrovsk Oblast
    • Dnipro, Dnipropetrovsk Oblast, Ukraine, 49102
      • City Clinical Hosp.4 of DCC ( Site 2102)
    • Kryviy Rih, Dnipropetrovsk Oblast, Ukraine, 50048
      • MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2101)
  • Ivano-Frankivsk Oblast
    • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
      • MI Precarpathian Clinical Oncology Center ( Site 2105)
  • Kharkivs’ka Oblast’
    • Kharkiv, Kharkivs’ka Oblast’, Ukraine, 61070
      • Communal non profit enterprise Regional Clinical Oncology Center ( Site 2112)
  • Kyivska Oblast
    • Khodosovka, Kyivska Oblast, Ukraine, 08173
      • Medical Center Asklepion LLC ( Site 2115)
    • Kyiv, Kyivska Oblast, Ukraine, 03022
      • Clinic of National Cancer Institute ( Site 2104)
    • Kyiv, Kyivska Oblast, Ukraine, 03126
      • Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2114)
  • Lviv Oblast
    • Lviv, Lviv Oblast, Ukraine, 79031
      • Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2106)
  • Odesa Oblast
    • Odesa, Odesa Oblast, Ukraine, 65055
      • MI Odessa Regional Oncological Centre ( Site 2108)
  • Zaporizhzhia Oblast
    • Zaporizhzhya, Zaporizhzhia Oblast, Ukraine, 69104
      • Medical Centre LLC Oncolife ( Site 2103)
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden NHS Foundation Trust ( Site 1512)
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital NHS Foundation Trust ( Site 1503)
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Cancer Centre ( Site 1507)
  • Walsall, United Kingdom, WS2 9PS
    • Manor Hospital Walsall England ( Site 1515)
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3NE
      • Royal Hospital in Derby ( Site 1514)
  • Dundee City
    • Dundee, Dundee City, United Kingdom, DD1 9SY
      • Ninewells Hospital and Medical School ( Site 1504)
  • East Riding Of Yorkshire
    • Cottingham, East Riding Of Yorkshire, United Kingdom, HU16 5JQ
      • Castle Hill Hospital ( Site 1501)
  • London, City of
    • London, London, City of, United Kingdom, NW1 2PG
      • University College London Hospital NHS Foundation Trust ( Site 1508)
    • London, London, City of, United Kingdom, SW17 0QT
      • St Georges University Hospitals NHS Foundation Trust. ( Site 1500)
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital ( Site 1510)
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0045)
    • Monterey, California, United States, 93940
      • Pacific Cancer Care ( Site 0063)
    • Orange, California, United States, 92868
      • UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0050)
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center - Plantation ( Site 0026)
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Southeastern Regional Medical Center, Inc. ( Site 0058)
  • Illinois
    • Zion, Illinois, United States, 60099
      • Midwestern Regional Medical Center, Inc. ( Site 0059)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center ( Site 0070)
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute [Boston, MA] ( Site 0010)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, PA ( Site 8001)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 0040)
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0071)
  • New York
    • Harrison, New York, United States, 10604
      • Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 0065)
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center ( Site 0017)
    • Rochester, New York, United States, 14642
      • University of Rochester ( Site 0041)
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute ( Site 0015)
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute ( Site 0042)
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • CTCA Southwestern ( Site 0060)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19124
      • Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0025)
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital ( Site 0053)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Hematology Oncology-Sioux Falls SD ( Site 0004)
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center ( Site 0001)
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 8000)
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance ( Site 0038)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Inclusion criteria include, but are not limited to:

• Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
• HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
• Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the site investigator
• Male participants must agree to use approved contraception
• Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
• 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 trial treatment
• Has a life expectancy of greater than 6 months
• Has adequate organ function

Exclusion Criteria:

Exclusion criteria include, but are not limited to:

• Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
• Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
• 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 active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
• Has an active infection requiring systemic therapy
• Has poorly controlled diarrhea
• Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has peripheral neuropathy > Grade 1
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
• A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
• Has active or clinically significant cardiac disease
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
• Has had an allogeneic tissue/solid organ transplant
• 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 co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137])

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Global Pembrolizumab + Standard of Care First Course; Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy.	Biological: Pembrolizumab; 200 mg on Day 1 of each 3-week cycle as an IV infusion.; Other Names: MK-3475; Keytruda®; Drug: Cisplatin; 80 mg/m^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.; Drug: 5-FU; 800 mg/m^2/day continuous on Days 1-5 of each 3-week cycle (120 hours or per local standard), administered as part of FP chemotherapy regimen.; Drug: Oxaliplatin; 130 mg/m^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.; Drug: Capecitabine; 1000 mg/m^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.; Biological: Trastuzumab; 8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.; Other Names: Herceptin®
Active Comparator: Global Standard of Care; Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy.	Drug: Cisplatin; 80 mg/m^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.; Drug: 5-FU; 800 mg/m^2/day continuous on Days 1-5 of each 3-week cycle (120 hours or per local standard), administered as part of FP chemotherapy regimen.; Drug: Oxaliplatin; 130 mg/m^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.; Drug: Capecitabine; 1000 mg/m^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.; Biological: Trastuzumab; 8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.; Other Names: Herceptin®; Biological: Placebo; Solution for IV infusion on Day 1 of each 3-week cycle.
Experimental: Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin; Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy.	Biological: Pembrolizumab; 200 mg on Day 1 of each 3-week cycle as an IV infusion.; Other Names: MK-3475; Keytruda®; Drug: Oxaliplatin; 130 mg/m^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.; Drug: S-1; Combination product of tegafur, CDHP, and Oxo. Oral capsules BID on Days 1-14 of each 3-week cycle based on body surface area (BSA): <1.25 m^2 BSA =40 mg, 1.25 to <1.5 m^2 BSA=50 mg, ≥1.5 m^2 BSA=60 mg. Administered as part of SOX chemotherapy regimen.; Biological: Trastuzumab; 8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.; Other Names: Herceptin®
Experimental: Japan Trastuzumab + S-1 Plus Oxaliplatin; Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy.	Drug: Oxaliplatin; 130 mg/m^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.; Drug: S-1; Combination product of tegafur, CDHP, and Oxo. Oral capsules BID on Days 1-14 of each 3-week cycle based on body surface area (BSA): <1.25 m^2 BSA =40 mg, 1.25 to <1.5 m^2 BSA=50 mg, ≥1.5 m^2 BSA=60 mg. Administered as part of SOX chemotherapy regimen.; Biological: Trastuzumab; 8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.; Other Names: Herceptin®; Biological: Placebo; Solution for IV infusion on Day 1 of each 3-week cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Per RECIST 1.1 Assessed by BICR	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. 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 progression. PFS was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.	Up to 46 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause. OS was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.	Up to 63 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 Assessed by BICR	ORR is defined as the percentage of participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by blinded independent central review (BICR). ORR was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.	Up to 63 months
Duration of Response (DOR) Per RECIST 1.1 Assessed by BICR	For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.	Up to 63 months
Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced an AE is reported for each treatment arm. Per statistical analysis plan, data from the second course of pembrolizumab was not included in the safety analysis.	Up to 63 months
Number of Participants Who Discontinued Study Treatment Due to AEs	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued study treatment due to an AE is reported for each treatment arm. Per statistical analysis plan, data from the second course of pembrolizumab was not included in the safety analysis.	Up to 63 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Janjigian YY, Kawazoe A, Yanez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. doi: 10.1038/s41586-021-04161-3. Epub 2021 Dec 15.
• Chung HC, Bang YJ, S Fuchs C, Qin SK, Satoh T, Shitara K, Tabernero J, Van Cutsem E, Alsina M, Cao ZA, Lu J, Bhagia P, Shih CS, Janjigian YY. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021 Feb;17(5):491-501. doi: 10.2217/fon-2020-0737. Epub 2020 Nov 10.
• Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. doi: 10.1016/S0140-6736(23)02033-0. Epub 2023 Oct 20.
• Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin S, Van Cutsem E, Tabernero J, Luo S, Mahave M, Tang Y, Lowery M, Monteiro MMF, Xu L, Shih CS, Sharan KP, Bhagia P, Rha SY. Pembrolizumab in HER2-Positive Gastric Cancer. N Engl J Med. 2024 Oct 10;391(14):1360-1362. doi: 10.1056/NEJMc2408121. Epub 2024 Sep 14. No abstract available.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Actual): March 20, 2024
• Study Completion (Actual): November 12, 2025

Study Registration Dates

• First Submitted: July 31, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Gastric Cancer; anti-PD-1; GEJ; programmed cell death receptor 1 (PD-1); programmed cell death ligand 1 (PD-L1); anti PD-1
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Platinum Compounds; Deoxyribonucleosides; Trastuzumab; Capecitabine; Oxaliplatin; Fluorouracil; Cisplatin; pembrolizumab; S 1 (combination)
• Other Study ID Numbers: 3475-811; MK-3475-811 (Other Identifier: MSD); 184142 (Registry Identifier: JAPAC-CTI); 2018-000224-34 (EudraCT Number); U1111-1297-9360 (Registry Identifier: UTN); 2023-508253-98-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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