Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer

To study treatment options for people with advanced non-small cell lung cancer that overexpresses a protein called HER2 and has not been treated yet in the metastatic setting. This study is comparing an investigational combination of a HER2-targeted treatment called trastuzumab deruxtecan plus an immunotherapy medication called pembrolizumab to the standard combination of chemotherapy plus pembrolizumab. The goal of the study is to understand how well these treatment approaches work and how safe they are when given as first-line treatment.

• Adults 18+ years of age
• Diagnosed with unresectable (cannot be removed by surgery), locally advanced (spread to nearby tissues) or metastatic (spread elsewhere in the body) non-squamous non-small cell lung cancer that overexpresses HER2 and has PD-L1 expression less than 50 percent
• Have not yet had systemic treatment for advanced cancer
• No gene changes with approved first-line therapies

• Receiving either a combination of a targeted antibody-drug called trastuzumab deruxtecan plus an immunotherapy drug (pembrolizumab) or standard chemotherapy plus pembrolizumab as their first treatment
• Regular clinic visits for treatment and monitoring