In patients with advanced PD-L1–negative nonsquamous non–small cell lung cancer (NSCLC) without targetable genomic alterations, first-line treatment with the Trop-2–directed antibody-drug conjugate sacituzumab tirumotecan plus pembrolizumab demonstrated a significant progression-free survival benefit over chemotherapy plus pembrolizumab, based on a prespecified interim analysis of the phase III OptiTROP-Lung06 trial. The findings were presented during the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract LBA66) and simultaneously published by Zhou et al in The New England Journal of Medicine.
“These results support the use of sacituzumab tirumotecan plus pembrolizumab as an active regimen for this population,” the investigators wrote.
Study Details
A total of 455 patients with previously untreated locally advanced or metastatic nonsquamous NSCLC without targetable genomic alterations and a PD-L1 tumor proportion score below 1% were randomly assigned in a 1:1 ratio to receive sacituzumab tirumotecan plus pembrolizumab (n = 229) or chemotherapy plus pembrolizumab (n = 226).
The primary endpoint was blinded independent central review–assessed progression-free survival. Overall survival was evaluated as a secondary endpoint.
Key Findings
At a median follow-up of 9.7 months, median progression-free survival was 15.0 months with sacituzumab tirumotecan plus pembrolizumab vs 5.7 months with chemotherapy plus pembrolizumab (hazard ratio [HR] = 0.49; P < .001). Objective response rates were 50.2% vs 47.3%, respectively, and median durations of response were 13.6 vs 6.8 months. Overall survival data were immature at the time of analysis (HR = 0.58; 95% confidence interval [CI] = 0.38–0.88).
Grade 3 or higher adverse events occurred in 47.6% of patients treated with sacituzumab tirumotecan plus pembrolizumab vs 60.6% of those who received chemotherapy plus pembrolizumab. Stomatitis was frequently reported with sacituzumab tirumotecan plus pembrolizumab, and most cases were grade 1 or 2.
“[Sacituzumab tirumotecan plus pembrolizumab] significantly prolonged [progression-free survival] vs [chemotherapy plus pembrolizumab], with longer response duration and a manageable safety profile,” the investigators concluded in their conference abstract.
Caicun Zhou, MD, of Shanghai East Hospital, China, and Junyou Ge, PhD, of the National Engineering Research Center of Targeted Biologics, Chengdu, are the corresponding authors of the article in The New England Journal of Medicine.
Disclosure: The study was funded by Sichuan Kelun-Biotech Biopharmaceutical. For full disclosures of the study authors, visit nejm.org.
