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

Phase 3

Recruiting

• Conditions: Gastric Cancer; Gastroesophageal Junction Cancer
• Interventions: Drug: Trastuzumab Deruxtecan; Drug: pembrolizumab; Drug: Trastuzumab; Drug: Chemotherapy

• Registration Number: NCT06731478
• Lead Sponsor: Daiichi Sankyo

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-09
• Study First Submitted QC: 2024-12-09
• Study First Posted: 2024-12-12
• Study Start: 2025-02-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-13
• Primary Completion: 2028-06-01
• Study Completion: 2030-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 726

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Main Cohort: Arm M1	Trastuzumab Deruxtecan	Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine) plus pembrolizumab
Main Cohort: Arm M1	pembrolizumab	Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine) plus pembrolizumab
Main Cohort: Arm M1	Chemotherapy	Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine) plus pembrolizumab
Main Cohort: Arm M2	pembrolizumab	Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) plus pembrolizumab
Main Cohort: Arm M2	Trastuzumab	Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) plus pembrolizumab
Main Cohort: Arm M2	Chemotherapy	Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) plus pembrolizumab
Exploratory Cohort: Arm E1	Trastuzumab Deruxtecan	Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine)
Exploratory Cohort: Arm E1	Chemotherapy	Participants will receive T-DXd plus fluoropyrimidine (5-FU or capecitabine)
Exploratory Cohort: Arm E2	Trastuzumab	Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine)
Exploratory Cohort: Arm E2	Chemotherapy	Participants will receive Trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine)

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	From date of randomization to the date of radiographic disease progression or death due to any cause, up to 59 months	PFS is defined as the time interval from the date of randomization to the date of radiographic disease progression as assessed by blinded independent central review (BICR) based on RECIST v1.1 or death due to any cause

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From date of randomization to the date of death due to any cause, up to 59 months	OS is defined as the time interval from the date of randomization to the date of death due to any cause

Trial Locations

Locations (5)

National Cancer Center Hospital; 🇯🇵 Chuo-ku, Japan

Gifu University Hospital; 🇯🇵 Gifu-shi, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa-shi, Japan

Kochi Health Sciences Center; 🇯🇵 Kochi-shi, Japan

Miyagi Cancer Center; 🇯🇵 Natori-shi, Japan