Datopotamab Deruxtecan Plus Pembrolizumab With or Without Platinum-Based Chemotherapy for Advanced or Metastatic NSCLC: The Phase Ib TROPION-Lung02 Trial

INTRODUCTION: The phase Ib two-part (dose escalation and expansion) six-cohort TROPION-Lung02 study evaluated datopotamab deruxtecan (Dato-DXd) plus pembrolizumab with or without platinum-based chemotherapy (Pt-CT) in patients with advanced or metastatic NSCLC without actionable genomic alterations. METHODS: ) once every 3 weeks. The primary objective was safety and tolerability; efficacy was a secondary objective. Exploratory biomarker analyses assessing TROP2 normalized membrane ratio by quantitative continuous scoring were performed in the treatment-naive patient subset. RESULTS: In total, 142 patients received doublet (n = 70) or triplet (n = 72) therapy; 96 were treatment-naive (doublet: n = 42; triplet: n = 54). Grade 3 or higher treatment-related adverse events occurred in 37.1% (doublet) and 59.7% (triplet) of patients. No treatment-related deaths occurred. In treatment-naive patients receiving doublet therapy, the confirmed objective response rate was 54.8%, the median duration of response was 20.1 months, and the median progression-free survival was 11.2 months. With triplet therapy, the confirmed objective response rate was 55.6%, the median duration of response was 13.7 months, and the median progression-free survival was 6.8 months. Tumor responses were observed across programmed death-ligand 1 expression levels for both regimens. Exploratory TROP2 normalized membrane ratio biomarker analyses revealed trends toward improved survival outcomes in patients who were biomarker-positive compared with biomarker-negative. CONCLUSION: Dato-DXd plus pembrolizumab therapy (with and without Pt-CT) exhibited appreciable safety and durable antitumor activity across programmed death-ligand 1 expression levels in patients with advanced or metastatic NSCLC. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT04526691.