DS8201-724 (DESTINY-Gastric05)
Research type
Research Study
Full 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)
IRAS ID
1011070
Contact name
Bettina Steffens
Contact email
Sponsor organisation
Daiichi Sankyo Inc.
Clinicaltrials.gov Identifier
Research summary
This is a Phase 3 study to evaluate the safety and efficacy of the combination of medications: trastuzumab deruxtecan, a fluoropyrimidine, and pembrolizumab, compared to standard of care chemotherapy with trastuzumab and pembrolizumab in participants with untreated, inoperable, locally advanced, or that has spread Human Epidermal Growth Factor Receptor 2 (HER2)- positive gastric or gastroesophageal junction (GEJ) cancer.
Though two performance studies, this clinical trial will also evaluate the safety and efficacy of the diagnostic tests used to assess biomarkers HER2 and PD-L1 (if required) to identify patients most likely to benefit from the study medications.
Participants will be tested for two biomarkers, HER2 and PD-L1, to determine their eligibility and the specific cohort they will join:
1. Main Cohort: T-DXd is combined with chemotherapy (5-FU or capecitabine) and pembrolizumab (immunotherapy) and compared to the standard treatment of trastuzumab with chemotherapy and pembrolizumab to check for safety and effectiveness.
2. Exploratory Cohort: T-DXd with chemotherapy is compared to trastuzumab with chemotherapy to study differences in safety and outcomes.
Participants are expected to be in this study for approximately 3 years. Their involvement will include:
3. Screening Period (approximately 28 days): It will determine if the participant meets the requirements to take part in the study.
4. Treatment: Study treatments will be administered via an intravenous (IV) infusion in 3-week (21 days) cycles. This means that it is given slowly through a needle, which will be inserted in a vein.
5. Follow-up: The follow-up period starts after the participant stops taking the study drug. Participants will have follow-up visits 40 days after stopping the study drug and long-term follow-up visits every 3 months.
Approximately 726 participants (approximately 576 participants in the Main Cohort and 150 participants in the Exploratory Cohort) worldwide will take part.REC name
London - Westminster Research Ethics Committee
REC reference
25/LO/0353
Date of REC Opinion
20 Jun 2025
REC opinion
Further Information Favourable Opinion