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OncoMatch/Clinical Trials/NCT06731478

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

Is NCT06731478 recruiting? Yes, currently enrolling (Sep 2026). This Phase 3 trial studies multiple treatments including Trastuzumab Deruxtecan and pembrolizumab for gastric cancer.

Phase 3RecruitingDaiichi SankyoNCT06731478Data as of Sep 2026Location: International · 26 countries

Treatment: Trastuzumab Deruxtecan · pembrolizumab · Trastuzumab · ChemotherapyThis 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.

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Extracted eligibility criteria

Treatments studied

Immunotherapy

pembrolizumab

Targeted therapy

Trastuzumab DeruxtecanTrastuzumab

Other

Chemotherapy

Cancer type

Gastric Cancer

Esophageal Carcinoma

Biomarker criteria

Required: HER2 (ERBB2) overexpression (IHC 3+ or IHC 2+/ISH-positive)

Centrally determined HER2-positive (IHC 3+ or IHC 2+/ISH-positive) gastric or GEJ cancer

Prior therapy

Cannot have received: HER2-targeted therapy

Prior exposure to other HER2-targeting therapies (including ADCs)

Lab requirements

Cardiac function

LVEF ≥50% within 28 days before randomization; no history of myocardial infarction within 6 months before randomization or symptomatic CHF (NYHA Class II-IV); QTcF ≤470 ms (females) or ≤450 ms (males)

LVEF ≥50% within 28 days before randomization. Medical history of myocardial infarction within 6 months before randomization or symptomatic CHF (NYHA Class II to IV) [excluded]. Has a corrected QT interval (QTcF) prolongation to >470 ms (females) or >450 ms (males)

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Yale Cancer Center · New Haven, Connecticut
  • Orchard Healthcare Research Inc. · Skokie, Illinois
  • University of Kansas Medical Center Research Institute, Inc. · Kansas City, Kansas
  • Maryland Oncology Hematology, P.A. · Silver Spring, Maryland
  • Tufts Medical Center · Boston, Massachusetts

Showing up to 5 US sites.

See all sites on ClinicalTrials.gov →

Frequently asked questions

Is NCT06731478 currently recruiting?

Yes, this trial is currently recruiting patients.

Are there prior therapy exclusions?

Yes. Prior HER2-targeted therapy disqualifies patients from enrollment.

Does this trial require ERBB2?

Yes, ERBB2 overexpression is a required biomarker for enrollment.

Could you qualify for this trial?

Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.

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