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

4 hours ago
  • #Clinical Trial
  • #NSCLC
  • #Immunotherapy
  • The phase Ib TROPION-Lung02 trial evaluated datopotamab deruxtecan (Dato-DXd) plus pembrolizumab with or without platinum-based chemotherapy (Pt-CT) in patients with advanced or metastatic NSCLC (amNSCLC).
  • Patients received Dato-DXd (4 or 6 mg/kg) plus pembrolizumab 200 mg alone (doublet) or with Pt-CT (triplet) every 3 weeks.
  • Primary objective was safety and tolerability; efficacy was secondary. Exploratory biomarker analyses assessed TROP2 normalized membrane ratio (NMR) in treatment-naive patients.
  • 142 patients received doublet (n=70) or triplet (n=72) therapy; 96 were treatment-naive.
  • Grade ≥3 treatment-related adverse events (TRAEs) occurred in 37.1% (doublet) and 59.7% (triplet) of patients. No treatment-related deaths occurred.
  • In treatment-naive patients, doublet therapy showed confirmed ORR of 54.8%, mDOR of 20.1 months, and mPFS of 11.2 months.
  • Triplet therapy showed confirmed ORR of 55.6%, mDOR of 13.7 months, and mPFS of 6.8 months.
  • Tumor responses were observed across PD-L1 expression levels for both regimens.
  • Exploratory TROP2 NMR biomarker analyses suggested improved survival outcomes in biomarker-positive patients.
  • Dato-DXd plus pembrolizumab therapy exhibited appreciable safety and durable antitumor activity across PD-L1 levels in amNSCLC patients.