PADL1NK-005 study design: a phase III trial of fetrastobart vedotin (Fetra-V) vs docetaxel in patients with previously treated tumor PD-L1–positive NSCLC

Fetrastobart vedotin (Fetra-V or PDL1V/PF-08046054) is an investigational antibody–drug conjugate that binds to programmed death ligand 1 (PD-L1)–expressing tumor cells and delivers a cytotoxic payload of monomethyl auristatin E. Fetra-V monotherapy has shown promising antitumor activity and manageable safety in patients with relapsed or refractory non-small cell lung cancer (NSCLC). PADL1NK-005 is a global, randomized, open-label phase III study assessing the efficacy and safety of Fetra-V monotherapy versus docetaxel in adults with PD-L1 ≥1% (utilizing locally tested PD-L1 expression using 22C3 or SP263 antibody clones) unresectable, locally advanced, or metastatic NSCLC following disease progression. Approximately 680 patients will be randomized 1:1 to receive Fetra-V 1.5 mg/kg using adjusted ideal body weight on days 1 and 8 of a 21-day cycle or docetaxel 75 mg/m2 on day 1 of a 21-day cycle. Randomization will be stratified by PD-L1 expression (1%–49% versus ≥50%), histology (nonsquamous versus squamous), select actionable genomic alterations (EGFR/ALK present versus absent/unknown), and Eastern Cooperative Oncology Group performance status (0 versus 1). The primary endpoint is overall survival in patients with PD-L1 ≥1% and PD-L1 ≥50%. Key secondary endpoints are progression-free survival and objective response rate by blinded independent central review in patients with PD-L1 ≥1% and PD-L1 ≥50%.Clinical trial registration NCT07144280 (https://clinicaltrials.gov/study/NCT07144280)