- 2026-01
- The New England journal of medicine 394(1)
- Wenfeng Fang
- Lin Wu
- Xiangjiao Meng
- Yu Yao
- Wei Zuo
- Wenxiu Yao
- Yanyan Xie
- Yu Zhang
- Jiuwei Cui
- Yongchang Zhang
- Xingya Li
- Wu Zhuang
- Jian Fang
- Qiming Wang
- Wei Jiang
- Kai Li
- Yuju Bai
- Yongzhong Luo
- Fang Ma
- Yan Yu
- Wei Zheng
- Zhentian Liu
- Bin Yang
- Rui Ma
- Yong Fang
- Runxiang Yang
- Liyan Jiang
- Jie Hu
- Jiacheng Yang
- Yina Diao
- Xiaoping Jin
- Junyou Ge
- Yunpeng Yang
- Li Zhang
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 376
- Population
- patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy
- Methods
- phase 3 trial, patients randomly assigned in a 1:1 ratio to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy
- Blinding
- Double-blind
- Duration
- median follow-up of 18.9 months
- Funding
- Industry-funded
Background
Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 that has shown significant survival benefits in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) that has progressed after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy.Methods
In this phase 3 trial, we enrolled patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy. The patients were randomly assigned, in a 1:1 ratio, to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. The primary end point was progression-free survival as assessed by blinded independent review. Overall survival was a hierarchically tested key secondary end point. In the interim analysis of progression-free survival as assessed by blinded independent review, sac-TMT monotherapy met the prespecified criterion for significance (two-sided P<0.0001); we report here the prespecified final analysis of progression-free survival and the preplanned interim analysis of overall survival.Results
Overall, 376 patients underwent randomization, with 188 assigned to each group. After a median follow-up of 18.9 months, the median progression-free survival was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group (hazard ratio for disease progression or death, 0.49; 95% confidence interval [CI], 0.39 to 0.62). Overall survival was significantly longer with sac-TMT than with chemotherapy (hazard ratio for death, 0.60; 95% CI, 0.44 to 0.82; two-sided Pā=ā0.001); 18-month overall survival was 65.8% and 48.0%, respectively. Treatment-related adverse events of grade 3 or higher occurred in 58.0% of patients receiving sac-TMT and in 53.8% of those receiving chemotherapy, with the most common being a decreased neutrophil count (39.9% vs. 33.0%); treatment-related serious adverse events occurred in 9.0% and 17.6%, respectively.Conclusions
In patients with EGFR-mutated advanced or metastatic NSCLC that had progressed after previous EGFR-TKI therapy, progression-free survival and overall survival outcomes were significantly better with sac-TMT than with platinum-based chemotherapy. (Funded by Sichuan Kelun-Biotech Biopharmaceutical; OptiTROP-Lung04 ClinicalTrials.gov number, NCT05870319.).