Multinational phase 1b trial of datopotamab deruxtecan plus pembrolizumab with or without chemotherapy for A/M NSCLC

The multinational phase 1b TROPION-Lung02 trial evaluated datopotamab deruxtecan (Dato-DXd) plu pembrolizumab with or without platinum-based chemotherapy (Pt-CT) in patients with advanced or metastatic non-small cell lung cancer (A/M NSCLC) without actionable genomic alterations. Patients received Dato-DXd (4 or 6 mg/kg) plus pembrolizumab 200 mg alone (doublet) or with Pt-CT (triplet; carboplatin AUC 5 or cisplatin 75 mg/m²) once every three weeks. The primary objective was safety and tolerability. A total of 142 patients received doublet (n=70) or triplet (n=72) therapy; 96 were treatment-naïve (42 in the doublet group and 54 in the triplet group). Grade 3 or 4 treatment-related adverse events occurred in 37% of patients in the doublet group and 60% of patients in the triplet group; there were no grade 5 TRAEs. Among treatment-naïve patients receiving doublet therapy, the confirmed objective response rate was 55% with a median duration of response 13.7 months and median progression-free survival of 11.2 months. With triplet therapy confirmed ORR was 56%, with mDOR 13.7 months, and mPFS 6.8 months. Tumor responses were observed across PD-L1 expression levels for both regimens. Exploratory TROP2 normalized membrane ratio biomarker analyses showed trends toward improved survival outcomes in patients who were biomarker positive compared with biomarker negative. The authors conclude that among patients with A/M NSCLC, Dato-DXd plus pembrolizumab with or without Pt-CT showed favorable safety and durable antitumor activity