Multicenter phase 3 trial of addition of sacituzumab tirumotecan to first-line pembrolizumab for PD-L1-positive advanced NSCLC

Sacituzumab tirumotecan (sac-TMT) combined with PD-1 or PD-L1 inhibitors has shown promising antitumor activity as first-line therapy for non-small cell lung cancer (NSCLC) in early-phase studies. The phase 3 OptiTROP-Lung05 trial, at 68 centers in China evaluated the combination of sac-TMT with pembrolizumab as first-line therapy for patients with PD-L1 positive advanced NSCLC without targetable genomic alterations. Patients with ad PD-L1 tumor proportion score (TPS) of 1% or greater were randomized to receive sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205). The primary endpoint was progression-free survival, as assessed by blinded independent central review. At the prespecified interim analysis, conducted after a median follow-up of 10.5 months (IQR 8.7-12.5), the median progression-free survival was not reached with sac-TMT plus pembrolizumab versus 5.7 months with pembrolizumab alone (sHR 0.35; p<0.0001). The progression-free survival benefit was broadly consistent across subgroups, including patients with PD-L1 TPS of 1-49% (HR 0.28; 95% CI 0.19-0.41) and those with PD-L1 TPS of 50% or greater (0.47; 0.29-0.77). Grade 3 or higher treatment-emergent adverse events occurred in 55% of patients in the sac-TMT plus pembrolizumab group and 31% of patients in the pembrolizumab alone group. The authors conclude that among patients with PD-L1 positive advanced NSCLC without targetable genomc alteration, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone.