Fang Wenfeng, Li Xingya, Wang Qiming, Meng Xiangjiao, Zheng Wei, Sun Longhua, Yao Wenxiu, Zhuang Wu, Fan Yun, Zhuo Minglei, Luo Yongzhong, Zhang Zhiye, Song Xia, Yang Runxiang, Yang Jiacheng, Jin Xiaoping, Diao Yina, Ge Junyou, Zhang Li
Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Centre for Cancer, Guangzhou, China.
Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
BMJ. 2025 Jun 5;389:e085680. doi: 10.1136/bmj-2025-085680.
To compare the efficacy and safety of sacituzumab tirumotecan (sac-TMT) with docetaxel in patients with locally advanced or metastatic epidermal growth factor receptor (-mutated non-small cell lung cancer (NSCLC) after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.
Multicentre, open label, randomised controlled trial.
48 centres in China, 1 September 2023 to 31 December 2024.
137 adults (aged 18-75 years) with -mutated advanced or metastatic NSCLC after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.
Patients were randomly assigned (2:1) to receive sac-TMT (5 mg/kg) on days 1 and 15 of each four week cycle, or docetaxel (75 mg/m) on day 1 of each three week cycle. Patients in the docetaxel group were permitted to crossover to sac-TMT treatment on disease progression.
The primary endpoint was objective response rate as assessed by a blinded independent review committee (BIRC). The secondary endpoints included objective response rate assessed by the investigator; disease control rate, progression-free survival, time to response, and duration of response assessed by BIRC and the investigator; overall survival; and safety.
137 patients were randomised to receive sac-TMT (n=91) or docetaxel (n=46). Median follow-up was 12.2 months at the data cut-off for efficacy (31 December 2024). BIRC assessed objective response rate was significantly higher in the sac-TMT group (45% (41/91)) docetaxel (16% (7/45)), with a difference of 29% (95% confidence interval (CI) 15% to 43%; one sided P<0.001). Median progression-free survival was longer with sac-TMT than with docetaxel assessed by BIRC (6.9 2.8 months; hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001) and the investigator (7.9 2.8 months; hazard ratio 0.23, 0.15 to 0.36; one sided P<0.001). The 12 month overall survival rate was 73% with sac-TMT and 54% with docetaxel (hazard ratio 0.49, 0.27 to 0.88; one sided P=0.007). After adjustment for crossover using the rank-preserving structural failure time model, sac-TMT also showed improved overall survival (hazard ratio 0.36, 0.20 to 0.66). Grade ≥3 treatment related adverse events were less frequent with sac-TMT than with docetaxel (56% 72%), with no new safety signals identified.
Sac-TMT showed statistically significant and clinically meaningful improvements in objective response rate, progression-free survival, and overall survival compared with docetaxel, with a manageable safety profile in patients with -mutated locally advanced or metastatic NSCLC.
ClinicalTrials.gov NCT05631262.
比较赛托珠单抗替鲁莫泰坎（sac-TMT）与多西他赛在既往接受表皮生长因子受体（EGFR）酪氨酸激酶抑制剂和铂类化疗治疗失败的局部晚期或转移性EGFR突变非小细胞肺癌（NSCLC）患者中的疗效和安全性。
多中心、开放标签、随机对照试验。
中国48个中心，2023年9月1日至2024年12月31日。
137名年龄在18至75岁之间、既往接受EGFR酪氨酸激酶抑制剂和铂类化疗治疗失败的EGFR突变晚期或转移性NSCLC成年患者。
患者被随机分配（2:1）接受每四周周期第1天和第15天的sac-TMT（5 mg/kg），或每三周周期第1天的多西他赛（75 mg/m²）。多西他赛组患者在疾病进展时可交叉接受sac-TMT治疗。
主要终点是由盲法独立审查委员会（BIRC）评估的客观缓解率。次要终点包括研究者评估的客观缓解率；疾病控制率、无进展生存期、缓解时间和由BIRC及研究者评估的缓解持续时间；总生存期；以及安全性。
137名患者被随机分配接受sac-TMT（n = 91）或多西他赛（n = 46）。在疗效数据截止时（2024年12月31日），中位随访时间为12.2个月。BIRC评估的客观缓解率在sac-TMT组显著更高（45%（41/91）），而多西他赛组为16%（7/45），差异为29%（95%置信区间（CI）15%至43%；单侧P<0.001）。BIRC评估的sac-TMT组中位无进展生存期长于多西他赛组（6.9±2.8个月；风险比0.30，95%CI 0.20至0.46；单侧P<0.001），研究者评估结果也显示如此（7.9±2.8个月；风险比0.23，0.15至0.36；单侧P<0.001）。sac-TMT组12个月总生存率为73%，多西他赛组为54%（风险比0.49，0.27至0.88；单侧P = 0.007）。使用秩保持结构失效时间模型对交叉情况进行调整后，sac-TMT也显示总生存期有所改善（风险比0.36，0.20至0.66）。sac-TMT组≥3级治疗相关不良事件的发生率低于多西他赛组（56%对72%），未发现新的安全信号。
与多西他赛相比，sac-TMT在客观缓解率、无进展生存期和总生存期方面显示出具有统计学意义和临床意义的改善，在EGFR突变的局部晚期或转移性NSCLC患者中具有可管理的安全性。
ClinicalTrials.gov NCT05631262
