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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 (May 2026). This Phase 3 trial studies multiple treatments including Trastuzumab Deruxtecan and pembrolizumab for gastric cancer.

Phase 3RecruitingDaiichi SankyoNCT06731478Data as of May 2026

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

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

Required: PD-L1 (CD274) expression (CPS (Combined Positive Score) tested; no threshold specified)

tumor sample for tissue-based IHC staining to centrally determine HER2 expression, PD-L1 CPS, and other correlatives

Disease stage

Metastatic disease required

Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma

Prior therapy

No prior treatment (treatment-naive required)
Max 0 prior lines

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 symptomatic CHF (NYHA II-IV); no MI within 6 months; 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 (New York Heart Association Class II to IV). 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.

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 →

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