Lancet (London, England) · 2026
Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xiong Anwen, Yao Wenxiu, Zheng Wei, Yu Yan, Chen Peng, Zhong Hua, Ge Junyou, Wang Hui, Chen Bolin, Wang Haiyong, Fan Yun, Yang Yunpeng, Pu Xingxiang, Song Xia, Wang Qiming, Du Xiaobo, Huang Zhangzhou, Li Xingya, Luo Hui, Yao Yu, Yu Qitao, Su Cuiyun, He Lang, Jiang Guanming, Cui Jiuwei, Liu Chunling, Yi Tienan, Che Guowei, Liu Zhentian, Zhang Lemeng, Zhou Ming, Fang Yong, Wei Youneng, Qing Yan, Jin Xiaoping, Zhou Caicun
Аннотация
BACKGROUND: Sacituzumab tirumotecan (sac-TMT), a trophoblast cell-surface antigen 2-targeting antibody-drug conjugate, combined with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has shown promising antitumour activity as first-line therapy for non-small-cell lung cancer (NSCLC) in early-phase studies. Our aim was to evaluate the efficacy and safety of sac-TMT plus pembrolizumab as first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.
METHODS: In this randomised, open-label, phase 3 trial (OptiTROP-Lung05) conducted across 68 hospitals in China, eligible patients had locally advanced or metastatic NSCLC without targetable genomic alterations and a PD-L1 tumour proportion score (TPS) of 1% or greater. Patients were randomly assigned (1:1) to receive sac-TMT (4 mg/kg on days 1, 15, and 29) plus pembrolizumab (400 mg fixed dose on day 1), or pembrolizumab alone, administered intravenously every 6 weeks. The primary endpoint was progression-free survival, as assessed by blinded independent central review in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT06448312). Recruitment is complete, with the trial ongoing and the final analysis to be reported later.
FINDINGS: Between June 7, 2024, and March 27, 2025, 741 patients were screened and 413 eligible patients were randomly assigned to receive sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205). At the prespecified interim analysis, conducted after a median follow-up of 10·5 months (IQR 8·7-12·5), median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 months; stratified hazard ratio [HR] 0·35 [95% CI 0·26-0·47]; p<0·0001). The progression-free survival benefit was broadly consistent across subgroups, including patients with PD-L1 TPS of 1-49% (HR 0·28 [95% CI 0·19-0·41]) and those with PD-L1 TPS of 50% or greater (HR 0·47 [0·29-0·77]). Grade 3 or higher treatment-emergent adverse events occurred in 115 (55%) of 208 patients in the sac-TMT plus pembrolizumab group and 64 (31%) of 204 patients in the pembrolizumab group.
INTERPRETATION: Among patients with PD-L1-positive advanced NSCLC without targetable genomic alterations, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, sac-TMT plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.
FUNDING: Sichuan Kelun-Biotech Biopharmaceutical.
METHODS: In this randomised, open-label, phase 3 trial (OptiTROP-Lung05) conducted across 68 hospitals in China, eligible patients had locally advanced or metastatic NSCLC without targetable genomic alterations and a PD-L1 tumour proportion score (TPS) of 1% or greater. Patients were randomly assigned (1:1) to receive sac-TMT (4 mg/kg on days 1, 15, and 29) plus pembrolizumab (400 mg fixed dose on day 1), or pembrolizumab alone, administered intravenously every 6 weeks. The primary endpoint was progression-free survival, as assessed by blinded independent central review in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT06448312). Recruitment is complete, with the trial ongoing and the final analysis to be reported later.
FINDINGS: Between June 7, 2024, and March 27, 2025, 741 patients were screened and 413 eligible patients were randomly assigned to receive sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205). At the prespecified interim analysis, conducted after a median follow-up of 10·5 months (IQR 8·7-12·5), median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 months; stratified hazard ratio [HR] 0·35 [95% CI 0·26-0·47]; p<0·0001). The progression-free survival benefit was broadly consistent across subgroups, including patients with PD-L1 TPS of 1-49% (HR 0·28 [95% CI 0·19-0·41]) and those with PD-L1 TPS of 50% or greater (HR 0·47 [0·29-0·77]). Grade 3 or higher treatment-emergent adverse events occurred in 115 (55%) of 208 patients in the sac-TMT plus pembrolizumab group and 64 (31%) of 204 patients in the pembrolizumab group.
INTERPRETATION: Among patients with PD-L1-positive advanced NSCLC without targetable genomic alterations, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, sac-TMT plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.
FUNDING: Sichuan Kelun-Biotech Biopharmaceutical.