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

Conditions

• Gastric Cancer
• Gastroesophageal Junction Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Trastuzumab Deruxtecan — DRUG
  T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
• pembrolizumab — DRUG
  Pembrolizumab will be administered at a dose of 200 mg IV Q3W
• Trastuzumab — DRUG
  Trastuzumab will be administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg IV Q3W
• Chemotherapy — DRUG
  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.

Study Details

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.

Key Dates

Start date

Feb 27, 2025

Status verified

Mar 2026

Primary completion

Jun 1, 2028

Completion

Feb 1, 2030

Study Design

Enrollment

726 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

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

Primary Outcome Measure

Progression Free Survival (PFS) [ Time Frame: From date of randomization to the date of radiographic disease progression or death due to any cause, up to 59 months ]

Central Contacts

• Contact for Trial Information
  908-992-6400
  [email protected]

Locations (18)

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