NCT06731478

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

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)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 726 (estimated)
• Sponsor: Daiichi Sankyo · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Gastric Cancer
• Gastroesophageal Junction Cancer

Interventions

Type	Name	Description
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	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.

Timeline

• Start date: 2025-02-27
• Primary completion: 2028-06-01
• Completion: 2030-02-01
• First posted: 2024-12-12
• Last updated: 2026-03-16

Locations

250 sites across 26 countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Italy, Japan, Netherlands, Norway, Poland, Portugal, Romania, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, Vietnam

Regulatory

• FDA-regulated drug study