Study of TDXd, Chemotherapy, Pembrolizumab, and Trastuzumab in First-Line Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer

March 13, 2026 updated by: Daiichi Sankyo

A Multicenter, Randomized, Open-Label, Phase 3 Trial of Trastuzumab Deruxtecan (Enhertu®) Plus Chemotherapy Plus or Minus Pembrolizumab Versus Chemotherapy Plus Trastuzumab Plus or Minus Pembrolizumab as First-Line Treatment in Participants With Unresectable, Locally Advanced or Metastatic HER2-Positive Gastric Or Gastroesophageal Junction (GEJ) Cancer (Destiny-Gastric05)

This clinical trial is designed to assess the efficacy and safety of the triplet combination of trastuzumab deruxtecan (ENHERTU, T-DXd, DS-8201a) plus a fluoropyrimidine plus pembrolizumab versus standard of care (SoC) chemotherapy plus trastuzumab plus pembrolizumab as first-line therapy in participants with unresectable, locally advanced or metastatic HER2-positive tumor PD-L1 CPS ≥1 gastric or GEJ cancer in the Main Cohort. An Exploratory Cohort will also be evaluated to assess the efficacy and safety of T-DXd plus a fluoropyrimidine versus SoC chemotherapy plus trastuzumab in participants with unresectable, locally advanced or metastatic HER2-positive tumor PD-L1 CPS <1 gastric or GEJ cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

726

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Not yet recruiting
        • Instituto Médico Especializado Alexander Fleming
      • Buenos Aires, Argentina
        • Not yet recruiting
        • CEMIC Ciudad Autonoma
      • Córdoba, Argentina
        • Recruiting
        • Clinica Universitaria Privada Reina Fabiola
      • Mar del Plata, Argentina
        • Recruiting
        • Centro de Investigaciones Medicas Mar del Plata
      • Rosario, Argentina
        • Recruiting
        • Instituto Medico de la Fundacion Estudios Clinicos
  • Australia
      • Bedford Park, Australia
        • Recruiting
        • Flinders Medical Centre
      • Clayton, Australia
        • Recruiting
        • Monash Medical Centre Clayton
      • Douglas, Australia
        • Recruiting
        • Townsville University Hospital
      • North Melbourne, Australia
        • Recruiting
        • Peter MacCallum Cancer Centre
      • St Leonards, Australia
        • Recruiting
        • GenesisCare North Shore (Oncology)
      • Subiaco, Australia
        • Recruiting
        • St John of God Subiaco Hospital
      • Wollongong, Australia
        • Recruiting
        • Wollongong Hospital
  • Austria
      • Graz, Austria
        • Recruiting
        • Lkh - Universitaetsklinikum Graz
      • Innsbruck, Austria
        • Not yet recruiting
        • Medizinische Universitat Innsbruck
      • Vienna, Austria
        • Not yet recruiting
        • Medizinische Universität Wien
      • Vienna, Austria
        • Recruiting
        • St. Josef Krankenhaus Wien
      • Wiener Neustadt, Austria
        • Not yet recruiting
        • Landesklinikum Wiener Neustadt
  • Belgium
      • Anderlecht, Belgium
        • Recruiting
        • Institut Jules Bordet
      • Bruges, Belgium
        • Recruiting
        • AZ Sint-Lucas
      • Brussels, Belgium
        • Recruiting
        • Cliniques Universitaires Saint-Luc
      • Leuven, Belgium
        • Recruiting
        • UZ Leuven
      • Liège, Belgium
        • Not yet recruiting
        • Centre Hospitalier Universitaire de Liège
      • Namur, Belgium
        • Recruiting
        • CHU UCL Namur
  • Brazil
      • Brasília, Brazil
        • Recruiting
        • Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês
      • Brazil, Brazil
        • Recruiting
        • ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira Sao Paulo
      • Florianópolis, Brazil
        • Recruiting
        • CEPON - Centro de Pesquisas Oncológicas de Santa Catarina
      • Jaú, Brazil
        • Recruiting
        • Fundacao Doutor Amaral Carvalho
      • Natal, Brazil
        • Recruiting
        • Liga Norte-Rio-Grandense Contra O Câncer
      • Porto Alegre, Brazil
        • Recruiting
        • Hospital de Clinicas de Porto Alegre
      • Porto Alegre, Brazil
        • Recruiting
        • Hospital Sao Lucas da PUCRS
      • Recife, Brazil
        • Recruiting
        • IMIP - Instituto de Medicina Integral Professor Fernando Figueira
      • Ribeirão Preto, Brazil
        • Recruiting
        • Hospital das Clinicas FMRP-USP
      • Rio de Janeiro, Brazil
        • Recruiting
        • INCA - Instituto Nacional de Cancer
      • Salvador, Brazil
        • Recruiting
        • Obras Sociais Irmã Dulce - Hospital Santo Antônio
      • Sao Jose Rio Preto, Brazil
        • Recruiting
        • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
  • Canada
      • Laval, Canada, H7M 3L9
        • Withdrawn
        • Cite de La Sante de Laval
      • Mississauga, Canada, L5M 2N1
        • Not yet recruiting
        • Trillium Health Partners Credit Valley Hospital
      • Montreal, Canada, H3T 1M5
        • Not yet recruiting
        • St. Mary's Hospital
      • Sherbrooke, Canada
        • Not yet recruiting
        • CHUS - Hôtel-Dieu
      • Toronto, Canada
        • Not yet recruiting
        • University Health Network - Princess Margaret Cancer Centre
      • Toronto, Canada, M5G 1X5
        • Withdrawn
        • Mount Sinai Hospital
      • Toronto, Canada
        • Not yet recruiting
        • Sunnybrook Health Sciences Centre
      • Toronto, Canada, M5G 1X5
        • Not yet recruiting
        • Mount Sinai Hospital
  • Chile
      • Concepción, Chile
        • Recruiting
        • Biocenter
      • Rancagua, Chile
        • Recruiting
        • URUMED Spa
      • Region Del Maule, Chile
        • Recruiting
        • Centro de Investigación del Maule
      • Santiago, Chile
        • Recruiting
        • Centro de Estudios Clinicos SAGA
      • Santiago, Chile
        • Not yet recruiting
        • Hospital Clínico Universidad de Chile
      • Santiago, Chile
        • Recruiting
        • FALP - Fundación Arturo López Pérez
  • China
      • Beijing, China, 100191
        • Recruiting
        • Peking University Third Hospital
      • Beijing, China, 100142
        • Recruiting
        • Beijing Cancer hospital
      • Changzhou, China
        • Not yet recruiting
        • The First People's Hospital of Changzhou
      • Fuzhou, China
        • Recruiting
        • Fujian Cancer Hospital
      • Hangzhou, China
        • Recruiting
        • The First Affiliated Hospital of Zhejiang University school of medicine
      • Hangzhou, China
        • Recruiting
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Harbin, China
        • Recruiting
        • Harbin Medical University Cancer Hospital
      • Hefei, China
        • Recruiting
        • Anhui Provincial Cancer Hospital
      • Jinan, China
        • Recruiting
        • Shandong Cancer Hospital
      • Lanzhou, China
        • Not yet recruiting
        • Lanzhou University Second Hospital
      • Lanzhou, China
        • Recruiting
        • Gansu Provincial Cancer Hospital
      • Linyi, China
        • Recruiting
        • Linyi Cancer Hospital
      • Meizhou, China
        • Recruiting
        • Meizhou People's Hospital
      • Shenyang, China
        • Recruiting
        • Liaoning cancer Hospital & Institute
      • Suzhou, China
        • Recruiting
        • The Second Affiliated Hospital of Soochow University
      • Taiyuan, China
        • Recruiting
        • Shanxi Provincial Cancer Hospital
      • Taiyuan, China
        • Recruiting
        • Shanxi Provincial People's Hospital
      • Tianjin, China
        • Recruiting
        • Tianjin Medical University Cancer Institute & Hospital
      • Wuhan, China, 430079
        • Recruiting
        • Hubei Cancer Hospital
      • Wuxi, China
        • Recruiting
        • Wuxi 4th People's Hospital
      • Xi'an, China
        • Recruiting
        • The First Affiliated Hospital of Xian Jiaotong University
      • Xiamen, China
        • Not yet recruiting
        • The First Affiliated Hospital of Xiamen University
      • Xuhui District, China
        • Recruiting
        • Fudan University Shanghai Cancer Center
      • Xuzhou, China
        • Recruiting
        • Xuzhou Central Hospital
      • Yinchuan, China
        • Recruiting
        • General Hospital of Ningxia Medical University
      • Zhengzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhou University
      • Ürümqi, China
        • Recruiting
        • The Affiliated Cancer Hospital of Xinjiang Medical University
  • Czechia
      • Brno, Czechia
        • Recruiting
        • Masarykuv onkologicky ustav
      • Hradec Králové, Czechia
        • Recruiting
        • Fakultni nemocnice Hradec Kralove
      • Olomouc, Czechia
        • Recruiting
        • Fakultni nemocnice Olomouc
      • Prague, Czechia
        • Recruiting
        • Fakultni nemocnice v Motole
  • France
      • Avignon, France
        • Recruiting
        • Institut Sainte Catherine
      • Brest, France
        • Recruiting
        • CHU de Brest - Hopital de la Cavale Blanche
      • Dijon, France
        • Recruiting
        • Centre Georges Francois Leclerc
      • Grenoble, France
        • Recruiting
        • CHU Grenoble - Hôpital MICHALLON
      • Lille, France
        • Recruiting
        • Centre Oscar Lambret
      • Lyon, France
        • Recruiting
        • Hopital Prive Jean Mermoz
      • Montpellier, France
        • Recruiting
        • CHU Montpellier, Saint Eloi
      • Nantes, France
        • Recruiting
        • Chru De Nantes Hotel-Dieu
      • Paris, France
        • Recruiting
        • Hôpital Saint-Antoine
      • Paris, France
        • Recruiting
        • Hôpital Européen Georges Pompidou
      • Paris, France
        • Recruiting
        • Institut Mutualiste Montsouris
      • Pessac, France
        • Recruiting
        • CHU Bordeaux - Hôpital Haut-Lévêque
      • Poitiers, France
        • Recruiting
        • CHU Poitiers - Hôpital la Milétrie
      • Strasbourg, France
        • Recruiting
        • Institut de Cancérologie de Strasbourg Europe - ICANS
      • Suresnes, France
        • Recruiting
        • Hopital Foch
      • Toulouse, France
        • Recruiting
        • Hôpital Rangueil
  • Germany
      • Berlin, Germany
        • Not yet recruiting
        • Charité Universitätsmedizin Berlin - Campus Virchow-Klinikum
      • Berlin, Germany
        • Recruiting
        • Vivantes Klinikum im Friedrichshain
      • Chemnitz, Germany
        • Recruiting
        • Klinikum Chemnitz gGmbH
      • Dresden, Germany
        • Recruiting
        • Universitaetsklinikum Carl Gustav Carus TU Dresden
      • Frankfurt am Main, Germany
        • Recruiting
        • Universitaetsklinikum Frankfurt Goethe-Universitaet
      • Hamburg, Germany
        • Recruiting
        • Universitaetsklinikum Hamburg-Eppendorf
      • Heidelberg, Germany
        • Recruiting
        • Universitaetsklinikum Heidelberg
      • Leipzig, Germany
        • Recruiting
        • Universitaetsklinikum Leipzig Aoer
      • München, Germany
        • Not yet recruiting
        • Klinikum rechts der Isar der TU Muenchen
  • Italy
      • Catania, Italy
        • Recruiting
        • Presidio Ospedaliero Garibaldi Nesima
      • Florenze, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi
      • Genova, Italy
        • Recruiting
        • IRCCS Ospedale Policlinico San Martino
      • Milan, Italy
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milan, Italy
        • Recruiting
        • Ospedale San Raffaele
      • Milan, Italy
        • Not yet recruiting
        • Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
      • Modena, Italy
        • Not yet recruiting
        • A.O.U. Policlinico di Modena
      • Napoli, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria- Università Degli Studi Della Campania "Luigi Vanvitelli"
      • Padua, Italy
        • Recruiting
        • IOV - Istituto Oncologico Veneto IRCCS
      • Pisa, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Pisana
      • Ravenna, Italy
        • Recruiting
        • Azienda Unita Sanitaria Locale- Ravenna
      • Rome, Italy
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Rozzano, Italy
        • Recruiting
        • Istituto Clinico Humanitas
      • San Giovanni Rotondo, Italy
        • Recruiting
        • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Torino, Italy
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
      • Tricase, Italy
        • Recruiting
        • Azienda Ospedaliera Card. G. Panico
  • Japan
      • Bunkyō City, Japan
        • Recruiting
        • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
      • Chūōku, Japan
        • Recruiting
        • National Cancer Center Hospital
      • Gifu, Japan
        • Recruiting
        • Gifu University Hospital
      • Hiroshima, Japan
        • Recruiting
        • Hiroshima City Hiroshima Citizens Hospital
      • Kashiwa-shi, Japan
        • Recruiting
        • National Cancer Center Hospital East
      • Kitakyushu, Japan, 806-0034
        • Recruiting
        • JCHO Kyushu Hospital
      • Kochi, Japan
        • Recruiting
        • Kochi Health Sciences Center
      • Kōtoku, Japan, 135-8550
        • Recruiting
        • Cancer Institute Hospital Of JFCR
      • Matsuyama, Japan, 791-0280
        • Recruiting
        • NHO Shikoku Cancer Center
      • Nagoya, Japan
        • Recruiting
        • Aichi Cancer Center Hospital
      • Natori-shi, Japan
        • Recruiting
        • Miyagi Cancer Center
      • Niigata, Japan, 951-8566
        • Recruiting
        • Niigata Cancer Center Hospital
      • Osaka, Japan, 541-8567
        • Recruiting
        • Osaka International Cancer Institute
      • Osakasayama-shi, Japan, 589-8511
        • Recruiting
        • Kindai University Hospital
      • Sapporo, Japan, 060-8648
        • Recruiting
        • Hokkaido University Hospital
      • Suita-shi, Japan, 565-0871
        • Recruiting
        • Osaka University Hospital
      • Yokohama, Japan, 241-8515
        • Recruiting
        • Kanagawa Cancer Center
  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Antoni van Leeuwenhoek
      • Leeuwarden, Netherlands
        • Recruiting
        • Medisch Centrum Leeuwarden
      • Nijmegen, Netherlands
        • Recruiting
        • Radboudumc
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus Medisch Centrum
      • Tilburg, Netherlands
        • Not yet recruiting
        • ETZ Elisabeth
      • Utrecht, Netherlands
        • Recruiting
        • UMC Utrecht
  • Norway
      • Bergen, Norway
        • Recruiting
        • Haukeland University Hospital
      • Lørenskog, Norway
        • Recruiting
        • Akershus Universitetssykehus HF
      • Oslo, Norway
        • Recruiting
        • Oslo Universitetssykehus HF, Ullevål
      • Trondheim, Norway
        • Recruiting
        • St. Olavs Hospital Hf, Universitetssykehuset i Trondheim
  • Poland
      • Bielsko-Biala, Poland
        • Recruiting
        • Beskidzkie Centrum Onkologii im.Jana Pawla II
      • Koszalin, Poland
        • Not yet recruiting
        • Szpital Wojewodzki im. Mikolaja Kopernika
      • Poznan, Poland
        • Recruiting
        • Wielkopolskie Centrum Onkologii
      • Warsaw, Poland
        • Not yet recruiting
        • Warszawski Uniwersytet Medyczny
      • Warsaw, Poland
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej Curie Panstwowy Instytut Badawczy W Warszawie
  • Portugal
      • Braga, Portugal
        • Recruiting
        • Hospital de Braga
      • Guimarães, Portugal
        • Recruiting
        • Hospital da Senhora da Oliveira Guimaraes, E.P.E.
      • Lisbon, Portugal
        • Recruiting
        • Hospital da Luz
      • Lisbon, Portugal
        • Not yet recruiting
        • Fundação Champalimaud
      • Lisbon, Portugal
        • Not yet recruiting
        • Unidade Local de Saude de Santa Maria, E.P.E. - Hospital de Santa Maria
      • Porto, Portugal
        • Recruiting
        • Instituto Português de Oncologia do Porto Francisco Gentil, EPE
  • Romania
      • Bucharest, Romania
        • Recruiting
        • Institutul Clinic Fundeni
      • Cluj-Napoca, Romania
        • Recruiting
        • S.C Medisprof S.R.L
      • Cluj-Napoca, Romania
        • Recruiting
        • Institutul Oncologic "Prof. Dr. Ion Chiricuţă" Cluj Napoca
      • Craiova, Romania
        • Recruiting
        • Centrul de Oncologie Sfantul Nectarie Craiova
      • Iași, Romania
        • Recruiting
        • Institutul Regional de Oncologie Iasi
      • Ovidiu, Romania
        • Recruiting
        • S.C Ovidius Clinical Hospital S.R.L
      • Suceava, Romania
        • Recruiting
        • S.C. Sigmedical Services Srl
  • South Korea
      • Cheongju-si, South Korea
        • Recruiting
        • Chungbuk National University Hospital
      • Daegu, South Korea
        • Recruiting
        • Kyungpook National University Chilgok Hospital
      • Goyang-si, South Korea
        • Recruiting
        • National Cancer Center
      • Hwasun-gun, South Korea, 58128
        • Recruiting
        • Chonnam National University Hwasun Hospital
      • Incheon, South Korea, 21565
        • Recruiting
        • Gachon University Gil Medical Center
      • Jeonju, South Korea, 54907
        • Recruiting
        • Jeonbuk National University Hospital
      • Seongnam, South Korea, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
      • Seongnam-si, South Korea
        • Recruiting
        • CHA Bundang Medical Center, CHA University
      • Seoul, South Korea, 6351
        • Recruiting
        • Samsung Medical Center
      • Seoul, South Korea, 5505
        • Recruiting
        • Asan Medical Center
      • Seoul, South Korea
        • Recruiting
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, South Korea, 3722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea, 3080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 2841
        • Recruiting
        • Korea University Anam Hospital
  • Spain
      • Badalona, Spain
        • Not yet recruiting
        • ICO Badalona - Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain
        • Recruiting
        • Hospital del Mar
      • Barcelona, Spain
        • Recruiting
        • Hospital Clinic De Barcelona
      • Córdoba, Spain
        • Recruiting
        • Hospital Universitario Reina Sofia
      • Elche, Spain
        • Recruiting
        • Hospital General Universitario de Elche
      • L'Hospitalet de Llobregat, Spain
        • Not yet recruiting
        • ICO l'Hospitalet - Hospital Duran i Reynals
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Not yet recruiting
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain
        • Recruiting
        • Md Anderson Cancer Centre
      • Murcia, Spain
        • Recruiting
        • Hospital General Universitario Morales Meseguer
      • Málaga, Spain
        • Recruiting
        • Hospital Regional Universitario de Malaga
      • Oviedo, Spain
        • Not yet recruiting
        • Hospital Universitario Central de Asturias
      • Pamplona, Spain
        • Recruiting
        • Hospital Universitario de Navarra
      • Seville, Spain
        • Recruiting
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain
        • Recruiting
        • Hospital Clinico Universitario de Valencia
  • Taiwan
      • Kaohsiung City, Taiwan
        • Recruiting
        • Kaohsiung Chang Gung Memorial Hospital
      • Tainan, Taiwan
        • Recruiting
        • National Cheng Kung University Hospital
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
      • Taipei, Taiwan, 112201
        • Recruiting
        • Taipei Veterans General Hospital
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Chang Gung Memorial Hospital,Linkou
  • Thailand
      • Bangkoknoi, Thailand
        • Recruiting
        • Siriraj Hospital
      • Dusit, Thailand
        • Recruiting
        • Vajira Hospital
      • Hat Yai, Thailand
        • Recruiting
        • Songklanagarind Hospital
      • Laksi, Thailand
        • Recruiting
        • Chulabhorn Hospital
      • Pathum Wan, Thailand
        • Recruiting
        • King Chulalongkorn Memorial Hospital
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye)
        • Recruiting
        • Medical Park Seyhan Hospital
      • Ankara, Turkey (Türkiye)
        • Not yet recruiting
        • Ankara City Hospital
      • Ankara, Turkey (Türkiye)
        • Recruiting
        • Hacettepe University Medical Faculty
      • Ankara, Turkey (Türkiye)
        • Recruiting
        • Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
      • Diyarbakır, Turkey (Türkiye)
        • Recruiting
        • Dicle University, Medical Faculty
      • Erzurum, Turkey (Türkiye)
        • Recruiting
        • Ataturk University Medical Faculty
      • Istanbul, Turkey (Türkiye)
        • Not yet recruiting
        • Medipol University Medical Faculty
      • Istanbul, Turkey (Türkiye)
        • Recruiting
        • Goztepe Prof. Dr. Suleyman Yalcin City Hospital
      • Izmir, Turkey (Türkiye)
        • Not yet recruiting
        • İ.E.Ü. Medicalpoint İzmir Hastanesi
      • Samsun, Turkey (Türkiye)
        • Not yet recruiting
        • Medical Park Samsun Hastanesi
  • United Kingdom
      • Birmingham, United Kingdom
        • Not yet recruiting
        • Queen Elizabeth Hospital
      • Cardiff, United Kingdom
        • Not yet recruiting
        • Velindre Cancer Centre
      • Dundee, United Kingdom
        • Recruiting
        • Ninewells Hospital
      • Hull, United Kingdom
        • Recruiting
        • Castle Hill Hospital
      • Leeds, United Kingdom
        • Not yet recruiting
        • St James's University Hospital
      • London, United Kingdom
        • Recruiting
        • Sarah Cannon Research Institute UK
      • London, United Kingdom
        • Recruiting
        • University College London Hospitals
      • Londonderry, United Kingdom
        • Not yet recruiting
        • Altnagelvin Area Hospital
      • Manchester, United Kingdom
        • Recruiting
        • The Christie Hospital
      • Sutton, United Kingdom
        • Recruiting
        • Royal Marsden Hospital
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Not yet recruiting
        • Yale Cancer Center
    • Illinois
      • Skokie, Illinois, United States, 60077
        • Recruiting
        • Orchard Healthcare Research Inc.
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Not yet recruiting
        • University of Kansas Medical Center Research Institute, Inc.
    • Maryland
      • Silver Spring, Maryland, United States, 20904
        • Not yet recruiting
        • Maryland Oncology Hematology, P.A.
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Not yet recruiting
        • University of Michigan Comprehensive Cancer Center Michigan Medicine
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Withdrawn
        • Minnesota Oncology Hematology, P.A.
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center - MAIN
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Not yet recruiting
        • Penn State University Milton S. Hershey Medical Center
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Not yet recruiting
        • Prisma Health Cancer Institute, ITOR, CRU
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Withdrawn
        • Tennessee Oncology Nashville Midtown
    • Texas
      • Dallas, Texas, United States, 75235
        • Not yet recruiting
        • UT Southwestern Medical Center
      • Tyler, Texas, United States, 75702
        • Not yet recruiting
        • Texas Oncology, P.A. - Tyler
    • Virginia
      • Norfolk, Virginia, United States, 23502-1871
        • Not yet recruiting
        • Virginia Oncology Associates
      • Roanoke, Virginia, United States, 24014
        • Not yet recruiting
        • Blue Ridge Cancer Care
    • Washington
      • Wenatchee, Washington, United States, 98801
        • Withdrawn
        • Wenatchee Valley Hospital & Clinics
  • Vietnam
      • Hanoi, Vietnam
        • Not yet recruiting
        • Hanoi Oncology Hospital
      • Hanoi, Vietnam
        • Not yet recruiting
        • National Cancer Hospital
      • Ho Chi Minh City, Vietnam
        • Not yet recruiting
        • Cho Ray Hospital
      • Ho Chi Minh City, Vietnam
        • Not yet recruiting
        • Hcmc Oncology Hospital
      • HoChiMinh, Vietnam
        • Not yet recruiting
        • HCMC University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion

  1. Sign and date the Tissue Prescreening ICF, prior to HER2 and PD-L1 CPS central testing. Sign and date the Main Screening ICF, prior to the start of any trial-specific qualification procedures. Sign and date the Optional PGx ICF (included in the Main Screening ICF) prior to any PGx procedure.
  2. Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.

  3. Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma histologically confirmed by pathology report. Prior treatment in the perioperative and/or adjuvant setting is permissible, provided there is >6 months between the end of perioperative or neoadjuvant treatment and the diagnosis of recurrent disease.

    Note: Prior use of IO (ie, anti-PD-1/PD-L1) therapy in the (neo)adjuvant setting is allowed as long as there is >6 months between the end of IO therapy and the diagnosis of recurrent disease.

  4. Centrally determined HER2-positive (IHC 3+ or IHC 2+/ISH-positive) gastric or GEJ cancer as classified by the American Society of Clinical Oncology-College of American Pathologists for GC on a tumor biopsy as detected by prospective central test on new (core, incisional, excisional biopsy) or existing tumor tissue taken at the time of diagnosis of locally advanced or metastatic disease.

    Note: Archival samples taken from a previous diagnostic or surgical biopsy not previously irradiated can be accepted. Details pertaining to tumor tissue submission can be found in the Study Laboratory Manual.

  5. All participants must provide a tumor sample for tissue-based IHC staining to centrally determine HER2 expression, PD-L1 CPS, and other correlatives. The mandatory FFPE tumor sample can be from either the primary tumor or metastatic biopsy. Specimens with limited tumor content (as centrally determined) and cytology samples are inadequate for defining tumor HER2 and PD-L1 status.
  6. At least 1 target measurable lesion on CT or MRI, assessed by the investigator based on RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
  7. LVEF ≥50% within 28 days before randomization.

exclusion criteria

  1. Prior exposure to other HER2-targeting therapies (including ADCs).
  2. Lack of physiological integrity of the upper gastrointestinal tract (ie, severe Crohn disease that results in malabsorption) or malabsorption syndrome that would preclude feasibility of oral chemotherapy (ie, capecitabine).
  3. Known DPD enzyme deficiency. Note: Screening for DPD enzyme deficiency is required only in regions/countries where DPD testing is SoC and with unknown DPD status. For regions/countries where DPD testing is not SoC, local practice should be followed.
  4. Contraindications to trastuzumab, 5-FU, capecitabine, cisplatin, or oxaliplatin treatment as per local label.
  5. Medical history of myocardial infarction within 6 months before randomization or symptomatic CHF (New York Heart Association Class II to IV). Participants with troponin levels above ULN at Screening (as defined by the manufacturer) and without any myocardial infarction -related symptoms should have a cardiologic consultation during the Screening Period to rule out myocardial infarction.
  6. Has a corrected QT interval (QTcF) prolongation to >470 ms (females) or >450 ms (males) based on the average of the screening triplicate 12-lead ECG.
  7. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
  8. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Main Cohort: Arm M1
Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine) plus pembrolizumab
Drug: Trastuzumab Deruxtecan
T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
Other Names:
  • DS-8201a
  • T-DXd
  • ENHERTU®
Drug: Chemotherapy

For Arms M1 and E1: 5-FU or capecitabine will be administered.

For Arms M2 and E2: Cisplatin plus 5-FU or oxaliplatin plus capecitabine will administered.

Drug: pembrolizumab
Pembrolizumab will be administered at a dose of 200 mg IV Q3W
Other Names:
  • KEYTRUDA®
Experimental: Main Cohort: Arm M2
Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) plus pembrolizumab
Drug: Chemotherapy

For Arms M1 and E1: 5-FU or capecitabine will be administered.

For Arms M2 and E2: Cisplatin plus 5-FU or oxaliplatin plus capecitabine will administered.

Drug: Trastuzumab
Trastuzumab will be administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg IV Q3W
Drug: pembrolizumab
Pembrolizumab will be administered at a dose of 200 mg IV Q3W
Other Names:
  • KEYTRUDA®
Experimental: Exploratory Cohort: Arm E1
Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine)
Drug: Trastuzumab Deruxtecan
T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
Other Names:
  • DS-8201a
  • T-DXd
  • ENHERTU®
Drug: Chemotherapy

For Arms M1 and E1: 5-FU or capecitabine will be administered.

For Arms M2 and E2: Cisplatin plus 5-FU or oxaliplatin plus capecitabine will administered.
Experimental: Exploratory Cohort: Arm E2
Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine)
Drug: Chemotherapy

For Arms M1 and E1: 5-FU or capecitabine will be administered.

For Arms M2 and E2: Cisplatin plus 5-FU or oxaliplatin plus capecitabine will administered.

Drug: Trastuzumab
Trastuzumab will be administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg IV Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: From date of randomization to the date of radiographic disease progression or death due to any cause, up to 59 months
PFS is defined as the time interval from the date of randomization to the date of radiographic disease progression as assessed by blinded independent central review (BICR) based on RECIST v1.1 or death due to any cause
From date of randomization to the date of radiographic disease progression or death due to any cause, up to 59 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From date of randomization to the date of death due to any cause, up to 59 months
OS is defined as the time interval from the date of randomization to the date of death due to any cause
From date of randomization to the date of death due to any cause, up to 59 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daiichi Sankyo

Collaborators

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 27, 2025

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

February 1, 2030

Study Registration Dates

First Submitted

December 9, 2024

First Submitted That Met QC Criteria

December 9, 2024

First Posted (Actual)

December 12, 2024

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DS8201-724
  • KEYNOTE-G03 (Other Identifier: Merck Sharp & Dohme LLC)
  • MK-3475-G03 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

IPD Sharing Time Frame

Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

IPD Sharing Access Criteria

Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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