146TiP A phase II study of zelenectide pevedotin, a Bicycle Drug Conjugate, in patients with NECTIN4 amplified advanced/metastatic non-small cell lung cancer (NSCLC) (Duravelo-4)

treated locally advanced/metastatic EGFRm NSCLC, based on TROPION-Lung05 results and supported by data from TROPION-Lung01.Retrospective analyses from TROPION-Lung01 showed high TROP2 normalized membrane ratio (NMR) positivity (63%) in pts with non-squamous (nsq) NSCLC without AGA and an association with prolonged PFS versus those with TROP2 NMR negative disease in pts receiving Dato-DXd (Garassino et al.JTO 2024;19 [Suppl]:S2-S3).TROPION-Lung17 (NCT07291037) is evaluating efficacy and safety of Dato-DXd vs docetaxel in pts with prospectively selected TROP2 NMR positive nsq NSCLC without AGA.Trial design: TROPION-Lung17 is a randomised, phase III, open-label, sponsor-blind, multicentre trial.The study is enrolling 400 adults with Stage IIIB/IIIC, or IV, TROP2 NMR positive, nsq NSCLC without AGA, who had radiological progression after prior platinum-based CT and anti-PD-1/PD-L1 therapy (concurrent 1L or sequential 2L), 1 measurable lesion per RECIST 1.1, and ECOG PS of 0/1.Pts are being randomised 1:1 to Dato-DXd (6 mg/kg IV Q3W) or docetaxel (75 mg/m 2 IV Q3W), stratified by prior anti-PD-1/anti-PD-L1 therapy duration (<6 vs 6 months), and geographical region (US, Europe, Canada vs other geographic regions).Treatment will continue until disease progression per RECIST v1.1, unacceptable toxicity, or another discontinuation criterion is met.Dual primary endpoints are PFS (by blinded independent central review [BICR]) and OS.Secondary endpoints include objective response rate and duration of response by BICR, time to second progression or death (PFS2), patient-reported outcomes, and safety.Recruitment is open and ongoing.