2. Academic Validation
  3. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial

Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial

  • BMJ. 2025 Jun 5:389:e085680. doi: 10.1136/bmj-2025-085680.
Wenfeng Fang 1,  Xingya Li 2,  Qiming Wang 3 4,  Xiangjiao Meng 5,  Wei Zheng 6,  Longhua Sun 7,  Wenxiu Yao 8,  Wu Zhuang 9,  Yun Fan 10,  Minglei Zhuo 11,  Yongzhong Luo 12,  Zhiye Zhang 13,  Xia Song 14,  Runxiang Yang 15,  Jiacheng Yang 16,  Xiaoping Jin 16,  Yina Diao 16,  Junyou Ge 17,  Li Zhang 1
Affiliations

Affiliations

  • 1 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.
  • 2 Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3 Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
  • 4 Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China.
  • 5 Department of Thoracic Radiotherapy, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, China.
  • 6 Oncology Department, Shengjing Hospital of China Medical University, Shenyang, China.
  • 7 Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 8 Department of Thoracic Medical Oncology, Sichuan Cancer Hospital, Chengdu, China.
  • 9 Department of Thoracic Oncology, Fujian Cancer Hospital, Fuzhou, China.
  • 10 Department of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
  • 11 Department of Thoracic Oncology, Beijing Cancer Hospital, Beijing, China.
  • 12 Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha, China.
  • 13 Oncology Department, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
  • 14 Respiratory Department, Shanxi Cancer Hospital, Taiyuan, China.
  • 15 Department of Internal Medicine 2, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 16 Clinical Research Centre, Sichuan Kelun-Biotech Biopharmaceutical, Chengdu, China.
  • 17 National Engineering Research Centre of Targeted Biologics, Chengdu, China.
PMID: 40473437 DOI: 10.1136/bmj-2025-085680
Abstract

Objective: To compare the efficacy and safety of sacituzumab tirumotecan (sac-TMT) with docetaxel in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung Cancer (NSCLC) after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.

Design: Multicentre, open label, randomised controlled trial.

Setting: 48 centres in China, 1 September 2023 to 31 December 2024.

Participants: 137 adults (aged 18-75 years) with EGFR-mutated advanced or metastatic NSCLC after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.

Intervention: 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/m2) on day 1 of each three week cycle. Patients in the docetaxel group were permitted to crossover to sac-TMT treatment on disease progression.

Main outcome measures: 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.

Results: 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)) v 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 v 2.8 months; hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001) and the investigator (7.9 v 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% v 72%), with no new safety signals identified.

Conclusions: 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 EGFR-mutated locally advanced or metastatic NSCLC.

Trial registration: ClinicalTrials.gov NCT05631262.

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