Multinational phase 2 trial of datopotamab deruxtecan in advanced or metastatic NSCLC with actionable genomic alterations

Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed antibody-drug conjugate. The multinational phase 2 TROPION-Lung05 trial evaluated Dato-DXd in patients with advanced or metastatic non-small cell lung cancer with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy. Among 137 patients, 71.5% received at least three prior lines of therapy for advanced/metastatic disease. Patients received Dato-DXd 6 mg/kg once every 3 weeks. The objective response rate by blinded independent central review was 35.8% (95% CI 27.8 to 44.4), whereas the disease control rate was 78.8% (71.0-85.3). Grade ≥ 3 treatment-related adverse events occurred in 28.5% of patients. The median progression-free survival was 5.4 months (95% CI 4.7-7.0) and the median overall survival was 13.6 months (9.9-NE). The authors conclude that Dato-DXd) showed encouraging and durable antitumor activity in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations, without new safety signals.