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

This study is investigating new treatment options for a type of cancer that starts in the stomach or where the food pipe joins the stomach (called the gastroesophageal junction). This cancer has already spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable, locally advanced). A key feature for joining this study is that the cancer cells must have a specific protein called HER2 on their surface.

The research focuses on comparing different combinations of medicines. One main group of patients will receive an experimental combination that includes a drug called Trastuzumab Deruxtecan (also known as ENHERTU or T-DXd), along with chemotherapy, pembrolizumab, and trastuzumab. This will be compared to the current standard treatment, which typically involves chemotherapy, trastuzumab, and pembrolizumab. The study wants to find out if the new combination is more effective at treating the cancer and if it has an acceptable safety profile.

There's also a smaller, 'exploratory' part of the study. This part will look at Trastuzumab Deruxtecan plus a specific chemotherapy drug, comparing it to the standard chemotherapy and trastuzumab treatment in patients whose cancer has a slightly different characteristic (related to PD-L1 levels). By doing this, researchers hope to identify the best initial treatment approach for different patients with HER2-positive stomach or food pipe cancer.