Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (TROPION-Lung08)
Objective
The primary objective of the study is to compare the efficacy of Dato-DXd and pembrolizumab with pembrolizumab alone in terms of either Progression Free Survival (PFS) or Overall Survival (OS) for participants with advanced or metastatic NSCLC without actionable genomic alterations whose tumor has high programmed death-ligand 1 (PD-L1) expression (TPS ≥50%) and who have not previously received systemic therapy for advanced or metastatic NSCLC.
Study Arms
- Experimental: Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd)
- Active Comparator: Pembrolizumab
Eligibility
- Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
- Sign and date the Tissue Screening and Main Informed Consent Forms, prior to the start of any study-specific qualification procedures.
- Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
- Histologically documented NSCLC that meets all of the following criteria:
- Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition).
- Documented negative test results for epidermal growth factor receptor (EGFR), lymphoma kinase (ALK), and proto-oncogene1 (ROS1) actionable genomic alterations based on analysis of tumor tissue.
- No known actionable genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition factor (MET), or other actionable driver kinases with locally approved therapies.
- Has provided a formalin-fixed tumor tissue sample for the measurement of trophoblast cell surface protein 2 (TROP2) protein expression and for the assessment of other exploratory biomarkers.
- Tumor has high programmed death receptor-1 (PD-L1) expression (TPS ≥50%) as determined by PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay by central testing (minimum of 6 slides).
- Has an adequate treatment washout period before Cycle 1 Day 1.
- Measurable disease based on local imaging assessment using RECIST Version 1.1.
- Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
- Has a life expectancy of at least 3 months.
- Adequate bone marrow function within 7 days before randomization.
