Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate targeting trophoblast cell surface antigen 2, which has been shown to significantly extend the survival of patients with EGFR-mutant non-small cell lung cancer (NSCLC) who have progressed after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy.
Methods
In this phase III clinical trial, we included patients with locally advanced or metastatic non-squamous NSCLC with EGFR mutations who had progressed after prior EGFR-TKI treatment. Patients were randomly assigned in a 1:1 ratio to receive either sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. The primary endpoint was progression-free survival, assessed by independent blinded review experts. Overall survival was a key secondary endpoint in a stratified analysis. In the interim analysis of progression-free survival assessed by independent blinded review, sac-TMT monotherapy met the pre-specified significance criteria (two-sided P<0.0001); this report presents the pre-specified final analysis of progression-free survival and the pre-planned interim analysis of overall survival.
Results
A total of 376 patients were randomized, with 188 in each group. After a median follow-up of 18.9 months, the median progression-free survival in the sac-TMT group was 8.3 months, compared to 4.3 months in the chemotherapy group (hazard ratio for disease progression or death was 0.49; 95% confidence interval [CI] 0.39 to 0.62). The overall survival in the sac-TMT group was significantly longer than that in the chemotherapy group (hazard ratio for death was 0.60; 95% CI 0.44 to 0.82; two-sided P=0.001). The 18-month overall survival rates were 65.8% and 48.0%, respectively. Among patients receiving sac-TMT, 58.0% experienced treatment-related adverse events of grade 3 or higher, compared to 53.8% in the chemotherapy group, with the most common being neutropenia (39.9% vs. 33.0%); 9.0% of patients receiving sac-TMT experienced serious adverse events, compared to 17.6% in the chemotherapy group.