This study investigates the safety and effectiveness of combining two drugs, trastuzumab deruxtecan (T-DXd, also called Enhertu®) and pembrolizumab, versus using pembrolizumab with other chemotherapy drugs for adults with a type of lung cancer called non-small cell lung cancer (NSCLC). This cancer is advanced, meaning it has spread and cannot be removed by surgery. The study focuses on participants whose cancer cells have higher amounts of a protein called HER2 and a specific level of another protein, PD-L1. People are eligible if they haven't had other treatments for this cancer.

• Study Length: Participants receive treatment until the disease progresses or they experience side effects.
• Visits: Regular clinic visits are needed for monitoring and treatment.
• Risks: Side effects may include heart issues or lung problems.

To join, participants must be at least 18 years old, have a certain type of tumor, and provide a tissue sample for testing. Those with recent heart attacks or severe lung conditions are not eligible. This study helps determine the best first-line treatment for this kind of lung cancer.