Under construction – not a live service
Sign in
Taking people in CanadaPhase 3

Tests a targeted drug with chemotherapy and immunotherapy for HER2-positive stomach cancer

Tests a targeted antibody drug with chemotherapy in adults with advanced HER2-positive stomach cancer.

Key facts

Who runs it
Daiichi Sankyo
Where
Laval, Mississauga, Montreal, Sherbrooke, and Toronto, CanadaSee the 7 sitesAlso in 25 other countries, 242 sites
Trial code
Registry title
Study of TDXd, Chemotherapy, Pembrolizumab, and Trastuzumab in First-Line Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer
Status
Recruiting
Phase
Phase 3
People taking part
726 people, planned
Started
27 Feb 2025
Expected to end
1 Feb 2030
Type of study
Interventional, 4 groups
Treatments tested
  • Trastuzumab Deruxtecan
  • pembrolizumab
  • Trastuzumab
  • Chemotherapy
Record updated
10 August 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with HER2-positive stomach or gastroesophageal junction cancer that cannot be removed by surgery or has spread, and who have not had treatment for it yet.

Age
18 years or older
Sex
Women and men can join.
Disease stage
Stomach or gastroesophageal junction adenocarcinoma that cannot be removed by surgery, is locally advanced or has spread. It must be confirmed by a pathology report, and at least 1 lesion must be measurable on CT or MRI.
Earlier treatment
No earlier treatment for the advanced cancer. Earlier treatment before or after surgery is allowed if more than 6 months passed between its end and the return of the cancer. No earlier HER2-targeting therapy.
Biomarker or test result
HER2-positive tumor (IHC 3+ or IHC 2+/ISH-positive), tested centrally on a tumor sample. PD-L1 CPS 1 or higher for the Main Cohort, PD-L1 CPS below 1 for the Exploratory Cohort. Heart pumping function (LVEF) 50% or higher.

Main reasons for not taking part

  • Earlier HER2-targeting therapy, including antibody-drug conjugates
  • Heart attack within 6 months, or symptomatic heart failure (NYHA Class II to IV)
  • History of or current lung inflammation (ILD/pneumonitis), or other serious lung disease
  • Known DPD enzyme deficiency
  • Problems with the upper gut that would prevent taking oral chemotherapy, or a reaction that rules out trastuzumab or the chemotherapy drugs

The registry criteria, word for word

Show all 16 criteriaShow less

Who can take part

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • LVEF ≥50% within 28 days before randomization

Who cannot take part

  • Prior exposure to other HER2-targeting therapies (including ADCs)
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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
  • Contraindications to trastuzumab, 5-FU, capecitabine, cisplatin, or oxaliplatin treatment as per local label

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

  • Have you had medicine for the cancer (such as chemotherapy) since it was found that it cannot be removed by surgery or has spread?
  • Has your doctor told you that the cancer cannot be removed by surgery, or that it has spread to other parts of the body?
  • Has a test of your tumour shown that it is HER2-positive?
  • Have you ever had treatment that targets the HER2 protein, such as trastuzumab (Herceptin) or trastuzumab deruxtecan (Enhertu)?
  • Have you ever had inflammation or scarring of the lungs, such as pneumonitis or interstitial lung disease?
  • Have you had a heart attack in the last 6 months, or do you have heart failure with symptoms?

Where in Canada

Also in 25 other countries, 242 sites

  • Cite de La Sante de LavalLaval, CanadaNo longer taking part
  • Trillium Health Partners - Credit Valley HospitalMississauga, CanadaNot yet recruiting
  • St. Mary's HospitalMontreal, CanadaNot yet recruiting
  • CHUS - Hôtel-DieuSherbrooke, CanadaNot yet recruiting
  • Mount Sinai HospitalToronto, CanadaNot yet recruiting
  • Sunnybrook Health Sciences CentreToronto, CanadaTaking people
  • University Health Network - Princess Margaret Cancer CentreToronto, CanadaNot yet recruiting

About the trial

What the trial wants to find out

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.

The 4 groups in the trial

  • Main Cohort: Arm M1Treatment being tested

    Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine) plus pembrolizumab

    Treatment: Trastuzumab Deruxtecan, pembrolizumab, and Chemotherapy

  • Main Cohort: Arm M2Treatment being tested

    Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) plus pembrolizumab

    Treatment: pembrolizumab, Trastuzumab, and Chemotherapy

  • Exploratory Cohort: Arm E1Treatment being tested

    Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine)

    Treatment: Trastuzumab Deruxtecan and Chemotherapy

  • Exploratory Cohort: Arm E2Treatment being tested

    Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine)

    Treatment: Trastuzumab and Chemotherapy

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
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)
Plain-language title
Tests a targeted drug with chemotherapy and immunotherapy for HER2-positive stomach cancerGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Fit questions
Built from NCT06731478, who can take part
Record updated
10 August 2026