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

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.

NCT Number	NCT06731478
Lead Sponsor	Daiichi Sankyo Collaborators: Merck Sharp & Dohme LLC
Conditions	Gastric Cancer, Gastroesophageal Junction Cancer
Enrollment	726 participants
Start Date	2025-02-27
Primary Completion	2028-06-01 (estimated)
Study Completion	2030-02-01 (estimated)
Updated on ClinicalTrials.gov	2026-08-10