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)
- Conditions
- Gastroesophageal Junction AdenocarcinomaGastric Cancer, Adenocarcinoma
- Interventions
- Registration Number
- NCT04704934
- Lead Sponsor
- Daiichi Sankyo
- 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.
- Detailed Description
This study will assess the efficacy and safety of T-DXd compared with Ram + PTX in participants with HER2-positive (defined as immunohistochemistry \[IHC\] 3+ or IHC 2+/in situ hybridization \[ISH\]+) gastric or GEJ adenocarcinoma (based on \[American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy. Participants will be randomized 1:1 to either T-DXd or Ram + PTX treatment. The primary objective will assess overall survival. Secondary objectives will further assess progression-free survival, objective response rate, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of T-DXd.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 490
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ramucirumab + paclitaxel Ramucirumab Participants 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. Trastuzumab deruxtecan Trastuzumab deruxtecan Participants 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 Paclitaxel Participants 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.
- Primary Outcome Measures
Name Time Method Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel Time from date of randomization until death (due to any cause), up to approximately 36 months Overall survival (OS) is defined as the time from date of randomization until death from any cause.
- Secondary Outcome Measures
Name Time Method 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 Progression-free survival (PFS) is defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on Investigator assessment.
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 Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0.
Serum Concentrations for Trastuzumab Deruxtecan, total anti-HER2 antibody, and Active Metabolite MAAA-1181a Cycles 1-4 and subsequent cycles on Day 1 pre- and post-infusion (each cycle is 28 days) 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 Objective response rate (ORR) is defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator.
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 Duration of response (DoR) is defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment.
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 Disease control rate (DCR) is defined as the proportion of participants who achieved CR, PR, or stable disease (SD) for a minimum of 6 weeks during study treatment, based on Investigator assessment.
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, 40 day follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days) The immunogenicity of trastuzumab deruxtecan will be assessed.
Percentage of Participants Who Have Treatment-emergent ADAs Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, 40 day follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days) The immunogenicity of trastuzumab deruxtecan will be assessed.
Trial Locations
- Locations (156)
Instituto Medico Especializado Alexander Fleming
🇦🇷Colegiales, Caba, Argentina
IONC Instituto Oncologico de Cordoba - Fundacion Richardet Longo
🇦🇷Nueva Cordoba, Cordoba, Argentina
Exelsus
🇦🇷San Miguel De Tucumán, Tucumán, Argentina
Fundacion Cenit
🇦🇷Buenos Aires, Argentina
UCL St. Luc
🇧🇪Brussels, Belgium
Antwerp University Hospital
🇧🇪Edegem, Belgium
Pôle Hospitalier Jolimont
🇧🇪Haine-Saint-Paul, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
PERSONAL - Oncologia de Precisao e Personalizada
🇧🇷Belo Horizonte, Brazil
Hospital Sirio Libanes
🇧🇷Brasilia, Brazil
ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
🇧🇷Ijui, Brazil
Hospital Ernesto Dornelles
🇧🇷Porto Alegre, Brazil
SIM Centro de Investigacion Clinica
🇨🇱Temuco, Cautin, Chile
Fundacion Arturo Lopez Perez
🇨🇱Santiago, Region Metropolitana, Chile
Clinica San Carlos de Apoquindo
🇨🇱Santiago, Region Metropolitana, Chile
Anhui Provincial Hospital
🇨🇳Heifi, Anhui, China
Fujian Medical University - Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, Fuijan, China
Xiamen University - The First Affiliated Hospital
🇨🇳Xiamen, Fujian, China
The Sixth Affiliated Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
1Affiliated H of Sun Yat Sen U
🇨🇳Guangzhou, Guangdong, China
Hebei Medical Univ 4th Hosp
🇨🇳Shijiazhuang, Hebei, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Zhongnan univ Xiangya hosp
🇨🇳Changshan, Hunan, China
Jiangsu Province Hosp
🇨🇳Nanjing, Jiangsu, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
1st Hosp of China Medical Univ
🇨🇳Shenyang, Liaoning, China
Shandong Cancer Hospital & Institute
🇨🇳Jinan, Shandong, China
Zhongshan Hosp Fudan Univ
🇨🇳Shanghai, Shanghai, China
Shanghai First People's Hosp
🇨🇳Shanghai, Shanghai, China
Xinjiang Medical University - Cancer Hospital
🇨🇳Urumqi, Xinjiang, China
Zhejiang Medical University - Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Peking Univ 3rd Hosp
🇨🇳Beijing, China
The 1st Hospital of Jilin Univ
🇨🇳Changchun, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, China
Linyi Cancer Hospital
🇨🇳Linyi, China
1 Affiliated H of Nanchang U
🇨🇳Nanchang, China
Fudan University - Shanghai Cancer Center
🇨🇳Shanghai, China
CHU Besançon
🇫🇷Besancon, France
CHRU
🇫🇷Brest, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon Cedex 08, France
Hopital de la Timone
🇫🇷Marseille, France
Institut de Recherche en Cancerologie de Montpellier IRCM
🇫🇷Montpellier, France
Hopital Saint Antoine
🇫🇷Paris, France
L Institut Mutualiste Montsouris
🇫🇷Paris, France
Hopital Europeen G. Pompidou
🇫🇷Paris, France
Pharmacie ICLN
🇫🇷Saint-Priest-en-Jarez, France
Gustave Roussy, étage -1.
🇫🇷Villejuif, France
Charité-Unimedizin Berlin
🇩🇪Berlin, Germany
Uniklinikum Carl-Gustav-Carus
🇩🇪Dresden Sachsen, Germany
Evang. Klin. Essen-Mitte gGmbH
🇩🇪Essen, Germany
Ins. für klinische onk. Forschung
🇩🇪Frankfurt Am Main Hessen, Germany
Asklepios Tumorzentrum Altona
🇩🇪Hamburg, Germany
Häm-Onk. Praxis Eppendorf
🇩🇪Hamburg, Germany
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
Uni zu Koln-Unikl. Koln
🇩🇪Kln Nordrhein-westfalen, Germany
Universitares Krebszentrum
🇩🇪Leipzig, Germany
Magyar Honvedseg Egeszs. K
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai
🇭🇺Debrecen, Hungary
Pamela Youde Nethersole Eastern Hospital
🇭🇰Chai Wan, Hong Kong
Princess Margaret Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Tolna M. Balassa Janos Korhaz
🇭🇺Szekszard, Hungary
Soroka Univ Medical CTR
🇮🇱Be'er-Sheva Southern, Israel
Cork University Hospital
🇮🇪Cork, Ireland
Tallaght University Hospital
🇮🇪Dublin, Ireland
Beaumont Hospital
🇮🇪Dublin, Ireland
St James's Hospital
🇮🇪Dublin, Ireland
Davidoff Center
🇮🇱Petach Tikva, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
AOU Pisana
🇮🇹Barone, Italy
IRCC-FPO Candiolo
🇮🇹Candiolo, Italy
AOU Mater Domini
🇮🇹Catanzaro, Italy
San Raffaele Hospital
🇮🇹Milano, Italy
Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
The Cancer Institute Hospital of JFCR
🇯🇵Koto-Ku, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Osaka University Hospital
🇯🇵Suita, Japan
Istituto Europeo di Oncologia S.r.L Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini
🇮🇹Milan, Italy
Ospedale Niguarda
🇮🇹Milan, Italy
Azienda Ospedaliero-Universitaria di Modena
🇮🇹Modena, Italy
Aou Vanvitelli
🇮🇹Napoli, Italy
Istituto Oncologico Veneto
🇮🇹Padua, Italy
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Aichia, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Japan
Osaka International Cancer Institute
🇯🇵Chuo Ku, Japan
Gifu University Hospital
🇯🇵Gifu, Japan
Kindai University Hospital
🇯🇵Ōsaka-sayama, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Japan
Kochi Health Sciences Center
🇯🇵Kochi, Japan
Kyungpook Nat Uni Chilgok Hos
🇰🇷Daegu, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Seoul Nati Univ Bundang Hosp
🇰🇷Seongnam, Korea, Republic of
Centrul de Oncologie Sf. Nectarie
🇷🇴Craiova, Romania
SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
🇷🇺Chelyabinsk, Russian Federation
City Clinical Oncology Dispensary
🇷🇺Saint-Petersburg, Russian Federation
Private Medical Institution "Euromedservice"
🇷🇺St.Petersburg, Russian Federation
Korea Univ Anam Hosp
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Chonbuk National University Hospital - Jeonbuk Regional Cancer Center
🇰🇷Seoul, Korea, Republic of
Sklodowska-Curie Inst Oncology
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny im.Mikulicza-Radeckiego
🇵🇱Wroclaw, Poland
Hospital Sra da Oliveira
🇵🇹Creixomil E Mariz, Portugal
Instituto Portugues De Oncologia Do Porto Francisco Gentil, E.P.E.
🇵🇹Porto, Portugal
Republican Clinical Oncology Dispensary
🇷🇺Ufa, Russian Federation
C Hosp Tras Montes Alto Douro
🇵🇹Vila Real, Portugal
S.C. Oncopremium-Team SRL
🇷🇴Baia Mare, Romania
Institutul Oncologic Prof. Dr. Alexandru Trestiorean Bucuresti IOB
🇷🇴Bucharest, Romania
S.C. Medisprof SRL
🇷🇴Cluj-Napoca, Romania
National Univ Cancer Inst SGP
🇸🇬Singapore, Singapore
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
H. Clinico U. de Valencia
🇪🇸Valencia, Spain
KMUH
🇨🇳Kaohsiung, Taiwan
CGMF-Kaohsiung Branch
🇨🇳Kaohsiung, Taiwan
China Medical Univ Hosp
🇨🇳Taichung, Taiwan
National Cheng Kung Univ Hosp
🇨🇳Tainan, Taiwan
National Taiwan University Hospital NTUH
🇨🇳Taipei, Taiwan
MacKay Memorial Hospital
🇨🇳Taipei, Taiwan
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
H. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp Univ Ramón y Cajal
🇪🇸Madrid, Spain
Taipei Veterans General Hosp
🇨🇳Taipei, Taiwan
CGMF-Linkou Branch
🇨🇳Taoyuan, Taiwan
SBU Adana Sehir Hastanesi
🇹🇷Adana, Turkey
Trakya Universitesi Balkan
🇹🇷Edirne, Turkey
Suleyman Yalcin Seh. Hast.
🇹🇷Istanbul, Turkey
Christie Hospital
🇬🇧Manchester, United Kingdom
Inonu Uni. Turgut Ozal Tip
🇹🇷Malatya, Turkey
National Cancer Institute
🇺🇦Kyiv, Ukraine
MedicalCenter ASKLEPION LLC
🇺🇦Kyiv, Ukraine
LLC "Oncolife"
🇺🇦Zaporizhzhia, Ukraine
University Hospitals Birmingham UHB NHS Foundation Trust - Queen Elizabeth Hospital Birmingham QEHB
🇬🇧Birmingham, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Velindre NHS Trust - Velindre Cancer Centre VCC
🇬🇧Cardiff, United Kingdom
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
UCLH Trust
🇬🇧London, United Kingdom
Royal Marsden NHS
🇬🇧London, United Kingdom
University of Oxford, The Churchill Hospital
🇬🇧Oxford, United Kingdom
Royal Marsden Sutton
🇬🇧Sutton, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧West Yorkshire, United Kingdom