TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC
Benjamin Levy, Enriqueta Felip, Martin Reck, James Chih‐Hsin Yang, Federico Cappuzzo, Yasuto Yoneshima, Caicun Zhou, Siddhartha Rawat, Jingdong Xie, Priyanka Basak, Lu Xu, Jacob Sands
Abstract
Pembrolizumab monotherapy is a standard first-line treatment for PD-L1–high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGAs). However, few patients experience long-term disease control, highlighting the need for more effective therapies. Datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2–directed antibody-drug conjugate, showed encouraging safety and antitumor activity with pembrolizumab in advanced NSCLC. We describe the rationale and design of TROPION-Lung08, a Phase III study evaluating safety and efficacy of first-line Dato-DXd plus pembrolizumab versus pembrolizumab monotherapy in patients with advanced/metastatic NSCLC without AGAs and with PD-L1 tumor proportion score ≥50%. Primary end points are progression-free survival and overall survival; secondary end points include objective response rate, duration of response, safety and presence of antidrug antibodies. Clinical trial registration: NCT05215340 (ClinicalTrials.gov)