臨床研究等提出・公開システム

Japanese

Date of registration	Jan. 22, 2025
Last modified on	Jan. 22, 2025
Trial ID	jRCT2041240173

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

Contact for Scientific Queries	Name	Inoguchi Akihiro
	Affiliation	Daiichi Sankyo Co., Ltd.
	Address	1-2-58, Hiromachi, Shinagawa-ku, Tokyo
	Telephone	+81-3-6225-1111
	E-mail	dsclinicaltrial_jp@daiichisankyo.com
Contact for Public Queries	Name	Contact for Clinical Trial Information
	Affiliation	Daiichi Sankyo Co., Ltd.
	Address	1-2-58, Hiromachi, Shinagawa-ku, Tokyo
	Telephone	+81-3-6225-1111
	E-mail	dsclinicaltrial_jp@daiichisankyo.com

Recruitment status	Pending

Anticipated date of first enrollment		Mar. 01, 2025
Actual date of first enrollment
Target sample size		726
Study Type		Interventional
Study Design	allocation	randomized controlled trial
	masking	open(masking not used)
	control	active control
	assignment	parallel assignment
	purpose	treatment purpose
Key inclusion & exclusion criteria	Inclusion Criteria	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 anddate 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 hasbeen 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 deficiency should be conducted per local requirements. 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 currentILD/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).
	Age Minimum	18age old over
	Age Maximum	No limit
	Gender	Both
Health Condition(s) or Problem(s) Studied		Gastric Cancer, Gastroesophageal Junction Cancer
Intervention(s)		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) Drug: Pembrolizumab Pembrolizumab will be administered at a dose of 200 mg 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 administered. Experimental: Main Cohort: Arm M2 Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) plus pembrolizumab 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 administered. 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) 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: 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 administered.
Health Condition(s) Keyword
Intervention(s) Keyword
Health Condition(s) Code
Intervention(s) Code
Primary Outcome(s)		Progression Free Survival (PFS) [Time Frame: From date of randomization to the date ofradiographic 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 ofradiographic disease progression as assessed by blinded independent central review (BICR) based on RECIST v1.1 or death due to any cause
Secondary Outcome(s)		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

Primary Sponsor	Daiichi Sankyo Co., Ltd.

Source of Monetary Support / Secondary Sponsor
Secondary Sponsor

Source of Monetary Support
Secondary Sponsor

Name of Certified Review Board	Institutional Review Board of Gifu University Hospital
Address	1-1 Yanagido, Gifu City, Gifu
Telephone	+81-58-230-6017
E-Mail	chikenj@t.gifu-u.ac.jp
Approval Status	Not approval
Date of approval

Plan to share IPD	Yes
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/ Supporting Information: - Study Protocol - Statistical Analysis Plan (SAP) - Informed Consent Form (ICF) 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. 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. URL: https://vivli.org/ourmember/daiichi-sankyo/

Plan to share IPD

Yes

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/ Supporting Information: - Study Protocol - Statistical Analysis Plan (SAP) - Informed Consent Form (ICF) 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. 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. URL: https://vivli.org/ourmember/daiichi-sankyo/

Secondary ID(s)	NCT06731478
Issuing Authority	ClinicalTrials.gov

Countries of Recruitment（Except Japan）	Argentina/ Australia/Austria/Belgium/Brazil/Canada/Chile/China/Czechia/France/Germany/Ireland/Italy/Korea/Netherlands/Poland/Portugal/Romania/Spain/Taiwan/Thailand/Turkey/United Kingdom/United States/Vietnam