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
  • 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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