Multicenter phase 3 trial of first-line sacituzumab tirumotecan plus pembrolizumab in PD-L1-negative advanced NSCLC

Pembrolizumab plus platinum-based chemotherapy and pemetrexed is a widely used first-line option for patients with PD-L1-negative advanced nonsquamous non-small cell lung cancer (nsqNSCLC) without targetable genomic alteration, but outcomes are suboptimal. In the multicenter phase 3 OptiTROP-Lung06 trial in China, patients with previously untreated locally advanced or metastatic nsqNSCLC without targetable genomic alterations and a PD-L1 tumor proportion score less than 1% were randomized 1:1 to receive sacituzumab tirumotecan plus pembrolizumab (n=229) or chemotherapy plus pembrolizumab (n=226). The primary endpoint was progression-free survival as assessed by blinded independent central review. Results of a prespecified interim analysis have now been reported. At a median follow-up of 9.7 months, median progression-free survival was 15.0 months with sacituzumab tirumotecan plus pembrolizumab versus 5.7 months with chemotherapy plus pembrolizumab (HR 0.49; 95% CI 0.36-0.65); overall survival data were immature; the HR for death was 0.58 (95% CI 0.38-0.88). Adverse events of grade 3 or higher that occurred after the start of treatment were reported in 47.6% of patients with sacituzumab tirumotecan plus pembrolizumab and in 60.6% of patients with chemotherapy plus pembrolizumab. Stomatitis was common with sacituzumab tirumotecan plus pembrolizumab, but the events were predominantly grade 1 or 2. The authors conclude that among patients with PD-L1-negative advanced nsqNSCLC without targetable genomic alterations, first-line sacituzumab tirumotecan plus pembrolizumab led to significantly longer progression-free survival than chemotherapy plus pembrolizumab.