The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS <50% and advanced or metastatic NSCLC without actionable genomic alternations.~Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion. The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.
This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).