Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)
A Phase 3, Multicenter, 2-Arm Randomized, Open-Label Study of Trastuzumab Deruxtecan in Subjects With HER2-Positive Metastatic and/or Unresectable Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)
2 other identifiers
interventional
490
24 countries
156
Brief Summary
This study will evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with ramucirumab and paclitaxel (Ram + PTX) in participants with HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2021
Longer than P75 for phase_3
156 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 8, 2021
CompletedFirst Posted
Study publicly available on registry
January 12, 2021
CompletedStudy Start
First participant enrolled
May 21, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2026
January 12, 2026
January 1, 2026
5.3 years
January 8, 2021
January 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
Overall survival (OS) is defined as the time from date of randomization until death from any cause.
Time from date of randomization until death (due to any cause), up to approximately 36 months
Secondary Outcomes (8)
Progression-free Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
Time from date of randomization until first objective radiographic disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months
Objective Response Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
From start of treatment to date of documented disease progression, up to approximately 36 months
Duration of Response in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months
Disease Control Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
From start of treatment to date of documented disease progression, up to approximately 36 months
Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and Physical Examination Findings
From time subjects signs informed consent form up to 40 days after last study dose
- +3 more secondary outcomes
Study Arms (2)
Trastuzumab deruxtecan
EXPERIMENTALParticipants who will be randomized to receive a 6.4 mg/kg intravenous (IV) dose of trastuzumab deruxtecan once every 3 weeks on Day 1 of each 21-day cycle.
Ramucirumab + paclitaxel
ACTIVE COMPARATORParticipants who will be randomized to receive a 8 mg/kg IV dose of ramucirumab on Days 1 and 15 in combination with 80 mg/m\^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.
Interventions
6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle
8 mg/kg IV infusion on Days 1 and 15 of a 28-day cycle
Eligibility Criteria
You may qualify if:
- Adults (according to local regulation) and able to provide informed consent for study participation.
- Pathologically documented gastric and GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease).
- Progression on or after first-line therapy with a trastuzumab or approved trastuzumab biosimilar-containing regimen. Note: Prior neoadjuvant or adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy. Prior neoadjuvant or adjuvant therapy that does not include trastuzumab will not be counted as a line of therapy regardless of the progression status of the subject.
- Locally or centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen.
- Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening.
- Adequate bone marrow, renal, hepatic function, and blood clotting function within 14 days of randomization.
You may not qualify if:
- Use of anticancer therapy after trastuzumab-containing treatment
- Medical history of myocardial infarction (MI) within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV).
- Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to \>470 msec (female subjects) or \>450 msec (male subjects) based on average of the Screening triplicate12-lead ECG.
- Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of) pulmonary involvement at the time of Screening.
- Prior complete pneumonectomy.
- Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated.
- History of severe hypersensitivity reactions to either the T-DXd or inactive ingredients in T-DXd.
- History of severe hypersensitivity reactions to other monoclonal antibodies, including ramucirumab or to any of its excipients.
- Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
- Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an unexplained fever \>38.0°C during Screening visits or on the first scheduled day of dosing (at the discretion of the Investigator, participants with tumor fever may be enrolled), which in the Investigator's opinion might compromise the participant's participation in the study or affect the study outcome
- Clinically significant gastrointestinal disorder (eg, including hepatic disorders, bleeding, inflammation, occlusion, ileus, diarrhea Grade \>1, jaundice, intestinal paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction) in the opinion of Investigator
- Has history of receiving live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Daiichi Sankyolead
- AstraZenecacollaborator
Study Sites (156)
Instituto Medico Especializado Alexander Fleming
Colegiales, Buenos Aires F.D., C1426, Argentina
IONC Instituto Oncologico de Cordoba - Fundacion Richardet Longo
Nueva Cordoba, Córdoba Province, 5000, Argentina
Exelsus
San Miguel de Tucumán, Tucumán Province, 4000, Argentina
Fundacion Cenit
Buenos Aires, C1125 ABD, Argentina
UCL St. Luc
Brussels, 1200, Belgium
Antwerp University Hospital
Edegem, 2650, Belgium
Pôle Hospitalier Jolimont
Haine-Saint-Paul, 7100, Belgium
UZ Leuven
Leuven, 3000, Belgium
PERSONAL - Oncologia de Precisao e Personalizada
Belo Horizonte, 30130-090, Brazil
Hospital Sirio Libanes
Brasília, 70200-730, Brazil
ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
Ijuí, 98700-000, Brazil
Hospital Ernesto Dornelles
Porto Alegre, 90160-092, Brazil
SIM Centro de Investigacion Clinica
Temuco, Cautin, 4810469, Chile
Fundacion Arturo Lopez Perez
Santiago, Santiago Metropolitan, 7500921, Chile
Clinica San Carlos de Apoquindo
Santiago, Santiago Metropolitan, 7550000, Chile
Anhui Provincial Hospital
Heifi, Anhui, 230001, China
Fujian Medical University - Fujian Provincial Cancer Hospital
Fuzhou, Fuijan, 350014, China
Xiamen University - The First Affiliated Hospital
Xiamen, Fujian, 361003, China
The Sixth Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510655, China
1Affiliated H of Sun Yat Sen U
Guangzhou, Guangdong, China
Hebei Medical Univ 4th Hosp
Shijiazhuang, Hebei, 50010, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450018, China
Zhongnan univ Xiangya hosp
Changshan, Hunan, 410008, China
Jiangsu Province Hosp
Nanjing, Jiangsu, China
Liaoning Cancer Hospital
Shenyang, Liaoning, 110042, China
1st Hosp of China Medical Univ
Shenyang, Liaoning, China
Shandong Cancer Hospital & Institute
Jinan, Shandong, 250117, China
Zhongshan Hosp Fudan Univ
Shanghai, Shanghai Municipality, 200000, China
Shanghai First People's Hosp
Shanghai, Shanghai Municipality, 200080, China
Xinjiang Medical University - Cancer Hospital
Ürümqi, Xinjiang, 830000, China
Zhejiang Medical University - Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Beijing Cancer Hospital
Beijing, 100142, China
Peking Univ 3rd Hosp
Beijing, 100191, China
The 1st Hospital of Jilin Univ
Changchun, 130031, China
Sir Run Run Shaw Hospital
Hangzhou, 310018, China
Linyi Cancer Hospital
Linyi, 276000, China
1 Affiliated H of Nanchang U
Nanchang, 330006, China
Fudan University - Shanghai Cancer Center
Shanghai, China
CHU Besançon
Besançon, 25000, France
CHRU
Brest, 29200, France
Centre Oscar Lambret
Lille, 59020, France
Centre Leon Berard
Lyon, 69373, France
Hopital de la Timone
Marseille, 13005, France
Institut de Recherche en Cancerologie de Montpellier IRCM
Montpellier, 34298, France
Hopital Saint Antoine
Paris, 75012, France
L Institut Mutualiste Montsouris
Paris, 75014, France
Hopital Europeen G. Pompidou
Paris, 75015, France
Pharmacie ICLN
Saint-Priest-en-Jarez, 42270, France
Gustave Roussy, étage -1.
Villejuif, 94800, France
Charité-Unimedizin Berlin
Berlin, 13353, Germany
Uniklinikum Carl-Gustav-Carus
Dresden Sachsen, 1307, Germany
Evang. Klin. Essen-Mitte gGmbH
Essen, 45136, Germany
Ins. für klinische onk. Forschung
Frankfurt Am Main Hessen, 60488, Germany
Häm-Onk. Praxis Eppendorf
Hamburg, 20249, Germany
Asklepios Tumorzentrum Altona
Hamburg, 22763, Germany
Uni zu Koln-Unikl. Koln
Kln Nordrhein-westfalen, D-50937, Germany
Universitares Krebszentrum
Leipzig, 4103, Germany
Pamela Youde Nethersole Eastern Hospital
Chai Wan, Hong Kong
Princess Margaret Hospital
Hong Kong, Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
The Chinese University of Hong Kong (CUHK) - Prince of Wales Hospital (PWH) - Vascular and Interventional Radiology Foundation (VIRF) Clinical Science Centre
Hong Kong, Hong Kong
Magyar Honvedseg Egeszs. K
Budapest, 1062, Hungary
Debreceni Egyetem Klinikai
Debrecen, 4032, Hungary
Tolna M. Balassa Janos Korhaz
Szekszárd, 7100, Hungary
Cork University Hospital
Cork, Ireland
Tallaght University Hospital
Dublin, 4835-044, Ireland
Beaumont Hospital
Dublin, 5000-508, Ireland
St James's Hospital
Dublin, Dublin 8, Ireland
Soroka Univ Medical CTR
Be'er-Sheva Southern, 84101, Israel
Davidoff Center
Petah Tikva, 49100, Israel
The Chaim Sheba Medical Center
Ramat Gan, 5265601, Israel
AOU Pisana
Barone, 56162, Italy
IRCC-FPO Candiolo
Candiolo, 10060, Italy
AOU Mater Domini
Catanzaro, 88100, Italy
Istituto Europeo di Oncologia S.r.L Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini
Milan, 20142, Italy
Ospedale Niguarda
Milan, 20162, Italy
San Raffaele Hospital
Milan, 20132, Italy
Istituto Nazionale dei Tumori
Milan, 20133, Italy
Azienda Ospedaliero-Universitaria di Modena
Modena, Italy
Aou Vanvitelli
Naples, 80131, Italy
Istituto Oncologico Veneto
Padua, 35128, Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa, 56126, Italy
Aichi Cancer Center Hospital
Nagoya, Aichia, 464-8681, Japan
National Cancer Center Hospital
Chūōku, 104-0045, Japan
Osaka International Cancer Institute
Chūōku, 541-8567, Japan
Gifu University Hospital
Gifu, 501-1194, Japan
National Cancer Center Hospital East
Kashiwa, 277-8577, Japan
Kobe City Medical Center General Hospital
Kobe, 650-0047, Japan
Kochi Health Sciences Center
Kochi, 781-8555, Japan
The Cancer Institute Hospital of JFCR
Kōtoku, 135-8550, Japan
National Hospital Organization Shikoku Cancer Center
Matsuyama, 791-0280, Japan
Niigata Cancer Center Hospital
Niigata, 951-8566, Japan
Kindai University Hospital
Ōsaka-sayama, 589-8511, Japan
Osaka University Hospital
Suita, 565-0871, Japan
Sklodowska-Curie Inst Oncology
Warsaw, 02-781, Poland
Uniwersytecki Szpital Kliniczny im.Mikulicza-Radeckiego
Wroclaw, 50-556, Poland
Hospital Sra da Oliveira
Creixomil E Mariz, 4200-072, Portugal
Instituto Portugues De Oncologia Do Porto Francisco Gentil, E.P.E.
Porto, 4200-072, Portugal
C Hosp Tras Montes Alto Douro
Vila Real, D24 NR0A, Portugal
S.C. Oncopremium-Team SRL
Baia Mare, 430295, Romania
Institutul Oncologic Prof. Dr. Alexandru Trestiorean Bucuresti IOB
Bucharest, 22328, Romania
S.C. Medisprof SRL
Cluj-Napoca, 400641, Romania
Centrul de Oncologie Sf. Nectarie
Craiova, 200542, Romania
SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
Chelyabinsk, 454087, Russia
Private Medical Institution "Euromedservice"
Saint Petersburg, 196604, Russia
City Clinical Oncology Dispensary
Saint Petersburg, 198255, Russia
Republican Clinical Oncology Dispensary
Ufa, 450054, Russia
National Univ Cancer Inst SGP
Singapore, 119228, Singapore
National Cancer Centre Singapore
Singapore, 169610, Singapore
Kyungpook Nat Uni Chilgok Hos
Daegu, 41404, South Korea
Chonnam National University Hwasun Hospital
Hwasun, 58128, South Korea
Seoul Nati Univ Bundang Hosp
Seongnam, 13620, South Korea
Korea Univ Anam Hosp
Seoul, 02841, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Seoul St. Marys Hospital
Seoul, 06591, South Korea
Chonbuk National University Hospital - Jeonbuk Regional Cancer Center
Seoul, 54907, South Korea
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Germans Trias i Pujol
Barcelona, 08916, Spain
H. Gregorio Maranon
Madrid, 28007, Spain
Hosp Univ Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital de Navarra
Pamplona, 31008, Spain
Hospital Clinico Universitario de Santiago de Compostela
Santiago de Compostela, 15706, Spain
H. Clinico U. de Valencia
Valencia, 46010, Spain
KMUH
Kaohsiung City, 80756, Taiwan
CGMF-Kaohsiung Branch
Kaohsiung City, 83301, Taiwan
China Medical Univ Hosp
Taichung, 40447, Taiwan
National Cheng Kung Univ Hosp
Tainan, 70457, Taiwan
National Taiwan University Hospital NTUH
Taipei, 10048, Taiwan
MacKay Memorial Hospital
Taipei, 10449, Taiwan
Taipei Veterans General Hosp
Taipei, 11217, Taiwan
CGMF-Linkou Branch
Taoyuan District, 33305, Taiwan
SBU Adana Sehir Hastanesi
Adana, 1330, Turkey (Türkiye)
Trakya Universitesi Balkan
Edirne, 22030, Turkey (Türkiye)
Suleyman Yalcin Seh. Hast.
Istanbul, 34722, Turkey (Türkiye)
Inonu Uni. Turgut Ozal Tip
Malatya, 44280, Turkey (Türkiye)
National Cancer Institute
Kyiv, 3022, Ukraine
MedicalCenter ASKLEPION LLC
Kyiv, 8173, Ukraine
LLC "Oncolife"
Zaporizhzhia, 69059, Ukraine
University Hospitals Birmingham UHB NHS Foundation Trust - Queen Elizabeth Hospital Birmingham QEHB
Birmingham, B15 2TH, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Velindre NHS Trust - Velindre Cancer Centre VCC
Cardiff, CF14 2TL, United Kingdom
Ninewells Hospital
Dundee, DD1 9SY, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L9 7BA, United Kingdom
UCLH Trust
London, NW1 2PG, United Kingdom
Royal Marsden NHS
London, SW3 6JJ, United Kingdom
Christie Hospital
Manchester, 8759, United Kingdom
University of Oxford, The Churchill Hospital
Oxford, OX3 7DQ, United Kingdom
Royal Marsden Sutton
Sutton, SM2 5PT, United Kingdom
Leeds Teaching Hospitals NHS Trust
West Yorkshire, LS9 7TF, United Kingdom
Related Publications (1)
Shitara K, Van Cutsem E, Gumus M, Lonardi S, de la Fouchardiere C, Coutzac C, Dekervel J, Hochhauser D, Shen L, Mansoor W, Liu B, Fornaro L, Ryu MH, Lee J, Faustino C, Metges JP, Tabernero J, Franke F, Janjigian YY, Souza F, Jukofsky L, Zhao Y, Kamio T, Zaanan A, Pietrantonio F; DESTINY-Gastric04 Trial Investigators. Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer. N Engl J Med. 2025 Jul 24;393(4):336-348. doi: 10.1056/NEJMoa2503119. Epub 2025 May 31.
PMID: 40454632DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Global Clinical Leader
Daiichi Sankyo
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 8, 2021
First Posted
January 12, 2021
Study Start
May 21, 2021
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2026
Last Updated
January 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Studies 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.
- Access Criteria
- Formal request from qualified scientific and medical researchers on IPD and clinical study documents from 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.
De-identified individual participant data (IPD) 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/