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RECRUITING

NCT06731478

PHASE3

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

Sponsor: Daiichi Sankyo

View on ClinicalTrials.gov

Summary

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.

Official title: 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)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

726

Start Date

2025-02-27

Completion Date

2030-02-01

Last Updated

2026-08-10

Healthy Volunteers

Conditions

Gastric Cancer Gastroesophageal Junction Cancer

Interventions

DRUG

Trastuzumab Deruxtecan

T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)

DRUG

pembrolizumab

Pembrolizumab will be administered at a dose of 200 mg IV Q3W

DRUG

Trastuzumab

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

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 be administered.

Inclusion Criteria 1. Sign and date the Tissue Prescreening ICF, prior to central HER2 and PD-L1 CPS 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. Centrally determined tumor PD-L1 CPS using the PD-L1 assay: * For the Main Cohort: PD-L1 CPS ≥1 * For the Exploratory Cohort: PD-L1 CPS \<1 6. 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 or new biopsy 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. 7. 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. 8. 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 for participants planned to be offered capecitabine as part of the study treatment. 3. Known total or partial 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. In Spain and Italy, screening for DPD enzyme deficiency is mandatory for all participants with unknown DPD status. 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).

Locations (250)

Yale Cancer Center

New Haven, Connecticut, United States

Orchard Healthcare Research Inc.

Skokie, Illinois, United States

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Maryland Oncology Hematology, P.A.

Silver Spring, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center Michigan Medicine

Ann Arbor, Michigan, United States

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

Memorial Sloan Kettering Cancer Center - MAIN

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Providence Portland Medical Center

Portland, Oregon, United States

Penn State University Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Prisma Health Cancer Institute, ITOR, CRU

Greenville, South Carolina, United States

Tennessee Oncology Nashville Midtown

Nashville, Tennessee, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Texas Oncology, P.A. - Tyler

Tyler, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Blue Ridge Cancer Care

Roanoke, Virginia, United States

Wenatchee Valley Hospital & Clinics

Wenatchee, Washington, United States

CEMIC Ciudad Autonoma

Buenos Aires, Argentina

Instituto Medico Especializado Alexander Fleming

Buenos Aires, Argentina

Clinica Universitaria Privada Reina Fabiola

Córdoba, Argentina

Centro de Investigaciones Medicas Mar del Plata

Mar del Plata, Argentina

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, Argentina

Flinders Medical Centre

Bedford Park, Australia

Monash Medical Centre Clayton

Clayton, Australia

Townsville University Hospital

Douglas, Australia

Peter MacCallum Cancer Centre

North Melbourne, Australia

GenesisCare North Shore (Oncology)

St Leonards, Australia

St John of God Subiaco Hospital

Subiaco, Australia

Wollongong Hospital

Wollongong, Australia

LKH - Universitaetsklinikum Graz

Graz, Austria

Medizinische Universität Innsbruck

Innsbruck, Austria

Medizinische Universität Wien

Vienna, Austria

St. Josef Krankenhaus Wien

Vienna, Austria

Landesklinikum Wiener Neustadt

Wiener Neustadt, Austria

Institut Jules Bordet

Anderlecht, Belgium

AZ Sint-Lucas

Bruges, Belgium

Cliniques Universitaires Saint-Luc

Brussels, Belgium

UZ Leuven

Leuven, Belgium

Centre Hospitalier Universitaire de Liege

Liège, Belgium

CHU UCL Namur

Namur, Belgium

Centro de Oncologia - Unidade Brasilia - Hospital Sirio Libanes

Brasília, Brazil

ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira Sao Paulo

Brazil, Brazil

CEPON - Centro de Pesquisas Oncológicas de Santa Catarina

Florianópolis, Brazil

Fundação Doutor Amaral Carvalho

Jaú, Brazil

Liga Norte-Rio-Grandense Contra o Câncer

Natal, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Brazil

IMIP - Instituto de Medicina Integral Professor Fernando Figueira

Recife, Brazil

Hospital das Clínicas FMRP-USP

Ribeirão Preto, Brazil

INCA - Instituto Nacional de Câncer

Rio de Janeiro, Brazil

Obras Sociais Irmã Dulce - Hospital Santo Antônio

Salvador, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

Sao Jose Rio Preto, Brazil

Cité de la Santé de Laval

Laval, Canada

Trillium Health Partners Credit Valley Hospital

Mississauga, Canada

St. Mary's Hospital

Montreal, Canada

CHUS - Hôtel-Dieu

Sherbrooke, Canada

Mount Sinai Hospital

Toronto, Canada

Mount Sinai Hospital

Toronto, Canada

Sunnybrook Health Sciences Centre

Toronto, Canada

University Health Network - Princess Margaret Cancer Centre

Toronto, Canada

Biocenter

Concepción, Chile

URUMED Spa

Rancagua, Chile

Centro de Investigacion del Maule

Region Del Maule, Chile

Centro de Estudios Clinicos SAGA

Santiago, Chile

FALP - Fundación Arturo López Pérez

Santiago, Chile

Hospital Clinico Universidad de Chile

Santiago, Chile

Beijing Cancer Hospital

Beijing, China

Peking University Third Hospital

Beijing, China

The First People's Hospital of Changzhou

Changzhou, China

Fujian Cancer Hospital

Fuzhou, China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, China

The First Affiliated Hospital of Zhejiang University school of medicine

Hangzhou, China

Harbin Medical University Cancer Hospital

Harbin, China

Anhui Provincial Cancer Hospital

Hefei, China

Shandong Cancer Hospital

Jinan, China

Gansu Provincial Cancer Hospital

Lanzhou, China

Lanzhou University Second Hospital

Lanzhou, China

Linyi Cancer Hospital

Linyi, China

Meizhou People's Hospital

Meizhou, China

Liaoning Cancer Hospital & Institute

Shenyang, China

The Second Affiliated Hospital of Soochow University

Suzhou, China

Shanxi Provincial Cancer Hospital

Taiyuan, China

Shanxi Provincial People's Hospital

Taiyuan, China

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

The Affiliated Cancer Hospital of Xinjiang Medical university

Ürümqi, China

Hubei Cancer Hospital

Wuhan, China

Wuxi 4th People's Hospital

Wuxi, China

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, China

The First Affiliated Hospital of Xiamen University

Xiamen, China

Fudan University Shanghai Cancer Center

Xuhui District, China

Xuzhou Central Hospital

Xuzhou, China

General Hospital of Ningxia Medical University

Yinchuan, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Masarykuv onkologicky ustav

Brno, Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, Czechia

Fakultni nemocnice Olomouc

Olomouc, Czechia

Fakultni nemocnice v Motole

Prague, Czechia

Institut Sainte Catherine

Avignon, France

CHU de Brest - Hopital de la Cavale Blanche

Brest, France

And 150 more locations on ClinicalTrials.gov

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (250)