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.

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.

我们的目标是评估sac-TMT联合帕博利珠单抗作为一线治疗方案对于PD-L1阳性、无可靶向基因组改变的晚期NSCLC患者的疗效和安全性。

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.

在这项在中国68家医院进行的随机、开放标签、III期试验（OptiTROP-Lung05）中，符合资格的患者患有局部晚期或转移性非小细胞肺癌（NSCLC），没有可靶向的基因组改变，并且肿瘤细胞比例评分（TPS）为1%或更高。

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.

患者被随机分配（1:1）接受sac-TMT（第1、15和29天各4 mg/kg）加派姆单抗（第1天固定剂量400 mg），或仅接受每6周一次静脉注射的派姆单抗。

The primary endpoint was progression-free survival, as assessed by blinded independent central review in the intention-to-treatpopulation.

主要终点是无进展生存期，通过盲法独立中央审查在意向治疗人群中评估。

This trial was registered with ClinicalTrials.gov (NCT06448312).

该试验已在ClinicalTrials.gov上注册（NCT06448312）。

Recruitment is complete, with the trial ongoing and the final analysis to be reported later.

招募工作已经完成，试验正在进行中，最终分析报告将在后期发布。

Results

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).

在2024年6月7日至2025年3月27日期间，共有741名患者接受了筛查，其中413名符合条件的患者被随机分配接受sac-TMT联合派姆单抗(n=208)或单独接受派姆单抗(n=205)治疗。

At the prespecified interim analysis, conducted after a median follow-up of 10·5 months (IQR 8·7-12·5), median progression-free survivalwas 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).

在预定的中期分析中，经过中位随访时间10.5个月（四分位数间距8.7-12.5个月），联合使用sac-TMT和pembrolizumab的无进展生存期显著长于仅使用pembrolizumab的（未达到vs 5.7个月；分层风险比[HR] 0.35 [95%置信区间0.26-0.47]；p<0.0001）。

The progression-free survivalbenefit 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]).

无进展生存期的获益在包括PD-L1 TPS为1-49%的患者（HR 0.28 [95%置信区间0.19-0.41]）和PD-L1 TPS为50%或更高的患者（HR 0.47 [0.29-0.77]）在内的多个亚组中广泛一致。

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.

在接受sac-TMT联合pembrolizumab治疗的208名患者中，有115名（55%）出现了3级或更高级别的治疗相关不良事件，而在仅接受pembrolizumab治疗的204名患者中，这一比例为64名（31%）。

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 survivalcompared with pembrolizumab alone.

在PD-L1阳性且无靶向基因组改变的晚期非小细胞肺癌患者中，一线治疗使用sac-TMT联合pembrolizumab相较于单独使用pembrolizumab，显著延长了无进展生存期。

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.

因此，sac-TMT联合派姆单抗有望重新定义对于没有可靶向基因改变的PD-L1阳性晚期非小细胞肺癌患者的前线治疗方案。

funding

Sichuan Kelun-Biotech Biopharmaceutical.

四川科伦生物制药。