Levy, Benjamin PBenjamin PLevyFelip, EnriquetaEnriquetaFelipReck, MartinMartinReckCHIH-HSIN YANGCappuzzo, FedericoFedericoCappuzzoYoneshima, YasutoYasutoYoneshimaZhou, CaicunCaicunZhouRawat, SiddharthaSiddharthaRawatXie, JingdongJingdongXieBasak, PriyankaPriyankaBasakXu, LuLuXuSands, JacobJacobSands2023-10-032023-10-032023-0714796694https://scholars.lib.ntu.edu.tw/handle/123456789/635918Pembrolizumab monotherapy is a standard first-line treatment for PD-L1-high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGA). 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).enDato-DXd; PD-1; PD-L1; TROP2; antibody–drug conjugate; datopotamab deruxtecan; immuno-oncology; non-small-cell lung cancer; pembrolizumab[SDGs]SDG3review10.2217/fon-2023-0230372490382-s2.0-85168221180https://api.elsevier.com/content/abstract/scopus_id/85168221180