Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies

  • J Hematol Oncol. 2025 Jun 6;18(1):61. doi: 10.1186/s13045-025-01705-2.
Quchang Ouyang  #  1 ,  Jordi Rodon  #  2 ,  Yan Liang  #  3 ,  Xinhong Wu  4 ,  Qun Li  5 ,  Lihua Song  6 ,  Min Yan  7 ,  Zhongsheng Tong  8 ,  YunPeng Liu  9 ,  Zev A Wainberg  10 ,  Ying Wang  11 ,  Cuizhi Geng  12 ,  Susanna V Ulahannan  13 ,  Guohua Yu  14 ,  Manish R Sharma  15 ,  Xiang Wang  16 ,  Judy S Wang  17 ,  Alexander Spira  18 ,  Weihong Zhao  19 ,  Rachel E Sanborn  20 ,  Ying Cheng  21 ,  Xian Wang  22 ,  Gesha Liu  23 ,  Yaling Li  23 ,  Junyou Ge  23 ,  Elliot Chartash  24 ,  Omobolaji O Akala  24 ,  Yongmei Yin  25
Affiliations
  • 1. Hunan Cancer Hospital, Changsha, China.
  • 2. University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 3. Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, 210029, China.
  • 4. Hubei Cancer Hospital, Wuhan, China.
  • 5. Shanghai East Hospital, Shanghai, China.
  • 6. Shandong Cancer Hospital, Jinan, China.
  • 7. The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
  • 8. Tianjin Cancer Hospital, Tianjin, China.
  • 9. The First Hospital of China Medical University, Shenyang, China.
  • 10. UCLA University of California Los Angeles, Santa Monica, CA, USA.
  • 11. Sun Yai-Sen Memorial Hospital, Guangzhou, China.
  • 12. The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • 13. Stephenson Cancer Center, University of Oklahoma/SCRI, Oklahoma City, OK, USA.
  • 14. Weifang People's Hospital, Weifang, China.
  • 15. START Center for Cancer Research - Midwest, Grand Rapids, MI, USA.
  • 16. Xuzhou Central Hospital, Xuzhou, China.
  • 17. Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA.
  • 18. Virginia Cancer Specialists (Fairfax), Fairfax, VA, USA.
  • 19. Chinese PLA General Hospital, Beijing, China.
  • 20. Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
  • 21. Jilin Cancer Hospital, Changchun, China.
  • 22. Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, China.
  • 23. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, China.
  • 24. Merck & Co., Inc., Rahway, NJ, USA.
  • 25. Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, 210029, China. [email protected].
  • # Contributed equally.
PMID: 40481574 DOI: 10.1186/s13045-025-01705-2
Abstract

Background: Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate composed of an anti-TROP2 monoclonal antibody coupled to a cytotoxic belotecan-derived Topoisomerase I inhibitor (KL610023) via a novel linker. We report results from the phase 1 dose-escalation cohorts in advanced solid tumors and phase 2 expansion cohorts for metastatic triple-negative breast Cancer (TNBC) from the first-in-human MK-2870-001 (KL264-01) study (NCT04152499).

Methods: Patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. In the phase 1 dose-escalation cohorts, patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. Sac-TMT was administered by intravenous administration every 2 weeks at 2 to 12 mg/kg. In phase 2, patients with TNBC and HR+/HER2- breast Cancer received sac-TMT per recommended doses for expansion (RDEs) identified in phase 1. Primary objectives were determining maximum tolerated dose (MTD) of sac-TMT and establishing RDEs (phase 1) and determining ORR per RECIST v1.1 by investigator assessment (phase 2). Adverse events were assessed per NCI-CTCAE version 5.0.

Results: Thirty patients were enrolled in phase 1 and received sac-TMT 2 mg/kg (n = 4), 4 mg/kg (n = 7), 5 mg/kg (n = 7), 5.5 mg/kg (n = 5), and 6 mg/kg (n = 7). Five patients had dose-limiting toxicities: grade 3 stomatitis at 4, 5.5, and 6 mg/kg; grade 3 rash at 5 mg/kg; and grade 3 urticaria at 6 mg/kg. MTD was 5.5 mg/kg and RDEs were 4 and 5 mg/kg. In the phase 2 dose expansion, ORR (95% CI) was 34.8% (16.4%, 57.3%) in the 4-mg/kg group (n = 23) and 38.9% (23.1%, 56.5%) in the 5-mg/kg group (n = 36) for TNBC. ORR (95% CI) was 31.7% (18.1%, 48.1%) for HR+/HER2- breast Cancer (n = 41).

Conclusions: Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor activity in metastatic TNBC and HR+/HER2 - breast Cancer. Sac-TMT is being investigated in phase 3 studies.

Trial registration: ClinicalTrials.gov, NCT04152499.

Keywords
Antibody–drug conjugate; HR+/HER2− breast cancer; Sac-TMT; Triple-negative breast cancer.
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