As reported in The Lancet by Xiong et al, an interim analysis of a Chinese phase III trial (OptiTROP-Lung05) has shown that the addition of sacituzumab tirumotecan (a trophoblast cell–surface antigen 2–targeting antibody-drug conjugate) to pembrolizumab significantly prolonged progression-free survival as first-line treatment in patients with PD-L1–positive advanced non–small cell lung cancer (NSCLC) without targetable genomic alterations.
Study Details
In the multicenter open-label trial, 413 patients with no targetable genomic alterations and a PD-L1 tumor proportion score of 1% or greater were randomly assigned between June 2024 and March 2025 to receive sacituzumab tirumotecan at 4 mg/kg on days 1, 15, and 29 of 6-week cycles plus pembrolizumab at a 400-mg fixed dose on day 1 of 6-week cycles (n = 208) or pembrolizumab at 400 mg alone every 6 weeks (n = 205). Treatment continued until disease progression. Pembrolizumab was administered for a maximum of 18 cycles. The primary endpoint was progression-free survival on blinded independent central review assessment in the intention-to-treat population.
Key Findings
At the prespecified interim analysis at a median follow-up of 10.5 months (interquartile range = 8.7–12.5 months), median progression-free survival was not reached (95% confidence interval [CI] = 13.6 months to not reached) in the sacituzumab tirumotecan plus pembrolizumab group vs 5.7 months (95% CI = 4.3–7.0 months) in the pembrolizumab-alone group (stratified hazard ratio [HR] = 0.35, 95% CI = 0.26–0.47, P < .0001). A progression-free survival benefit was observed both among patients with a PD-L1 tumor proportion score of 1% to 49% (HR = 0.28, 95% CI = 0.19–0.41) and among those with a PD-L1 tumor proportion score of 50% or greater (HR = 0.47, 95% CI = 0.29–0.77).
Grade 3 or higher adverse events occurred in 55% of the sacituzumab tirumotecan plus pembrolizumab group and 31% of the pembrolizumab-alone group, most commonly decreased neutrophil count (17% vs < 1%), anemia (9% vs 1%), decreased white blood cell count (9% vs < 1%), pneumonia (8% vs 5%), and stomatitis (5% vs 0%). Serious adverse events were reported in 39% vs 29% of patients. Adverse events led to discontinuation of treatment in 4% vs 5% of patients. Treatment-related adverse events led to death in one patient vs three patients.
The investigators concluded: “Among patients with PD-L1–positive advanced NSCLC without targetable genomic alterations, first-line treatment with [sacituzumab tirumotecan] plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, [sacituzumab tirumotecan] plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1–positive advanced NSCLC without targetable genomic alterations.”
Caicun Zhou, MD, of the Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, China, is the corresponding author for The Lancet article.
DISCLOSURE: The study was funded by Sichuan Kelun–Biotech Biopharmaceutical. For full disclosures of the study authors, visit thelancet.com.
