Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies
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 s...
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| Language: | English |
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BMC
2025-06-01
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| Series: | Journal of Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s13045-025-01705-2 |
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| author | Quchang Ouyang Jordi Rodon Yan Liang Xinhong Wu Qun Li Lihua Song Min Yan Zhongsheng Tong YunPeng Liu Zev A. Wainberg Ying Wang Cuizhi Geng Susanna V. Ulahannan Guohua Yu Manish R. Sharma Xiang Wang Judy S. Wang Alexander Spira Weihong Zhao Rachel E. Sanborn Ying Cheng Xian Wang Gesha Liu Yaling Li Junyou Ge Elliot Chartash Omobolaji O. Akala Yongmei Yin |
| author_facet | Quchang Ouyang Jordi Rodon Yan Liang Xinhong Wu Qun Li Lihua Song Min Yan Zhongsheng Tong YunPeng Liu Zev A. Wainberg Ying Wang Cuizhi Geng Susanna V. Ulahannan Guohua Yu Manish R. Sharma Xiang Wang Judy S. Wang Alexander Spira Weihong Zhao Rachel E. Sanborn Ying Cheng Xian Wang Gesha Liu Yaling Li Junyou Ge Elliot Chartash Omobolaji O. Akala Yongmei Yin |
| author_sort | Quchang Ouyang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-542c4c40c63a4772b52cf3c4d31ce9aa |
| institution | Kabale University |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-542c4c40c63a4772b52cf3c4d31ce9aa2025-08-20T03:26:43ZengBMCJournal of Hematology & Oncology1756-87222025-06-0118111310.1186/s13045-025-01705-2Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapiesQuchang Ouyang0Jordi Rodon1Yan Liang2Xinhong Wu3Qun Li4Lihua Song5Min Yan6Zhongsheng Tong7YunPeng Liu8Zev A. Wainberg9Ying Wang10Cuizhi Geng11Susanna V. Ulahannan12Guohua Yu13Manish R. Sharma14Xiang Wang15Judy S. Wang16Alexander Spira17Weihong Zhao18Rachel E. Sanborn19Ying Cheng20Xian Wang21Gesha Liu22Yaling Li23Junyou Ge24Elliot Chartash25Omobolaji O. Akala26Yongmei Yin27Hunan Cancer HospitalUniversity of Texas MD Anderson Cancer CenterJiangsu Province HospitalHubei Cancer HospitalShanghai East HospitalShandong Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalTianjin Cancer HospitalThe First Hospital of China Medical UniversityUCLA University of California Los AngelesSun Yai-Sen Memorial HospitalThe Fourth Hospital of Hebei Medical UniversityStephenson Cancer Center, University of Oklahoma/SCRIWeifang People’s HospitalSTART Center for Cancer Research - MidwestXuzhou Central HospitalFlorida Cancer Specialists/Sarah Cannon Research InstituteVirginia Cancer Specialists (Fairfax)Chinese PLA General HospitalEarle A. Chiles Research Institute, Providence Cancer InstituteJilin Cancer HospitalSir Run Run Shaw Hospital Zhejiang University School of MedicineSichuan Kelun-Biotech Biopharmaceutical Co., Ltd.Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.Merck & Co., Inc.Merck & Co., Inc.Jiangsu Province HospitalAbstract 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.https://doi.org/10.1186/s13045-025-01705-2Sac-TMTAntibody–drug conjugateTriple-negative breast cancerHR+/HER2− breast cancer |
| spellingShingle | Quchang Ouyang Jordi Rodon Yan Liang Xinhong Wu Qun Li Lihua Song Min Yan Zhongsheng Tong YunPeng Liu Zev A. Wainberg Ying Wang Cuizhi Geng Susanna V. Ulahannan Guohua Yu Manish R. Sharma Xiang Wang Judy S. Wang Alexander Spira Weihong Zhao Rachel E. Sanborn Ying Cheng Xian Wang Gesha Liu Yaling Li Junyou Ge Elliot Chartash Omobolaji O. Akala Yongmei Yin Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies Journal of Hematology & Oncology Sac-TMT Antibody–drug conjugate Triple-negative breast cancer HR+/HER2− breast cancer |
| title | Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies |
| title_full | Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies |
| title_fullStr | Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies |
| title_full_unstemmed | Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies |
| title_short | Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies |
| title_sort | results of a phase 1 2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies |
| topic | Sac-TMT Antibody–drug conjugate Triple-negative breast cancer HR+/HER2− breast cancer |
| url | https://doi.org/10.1186/s13045-025-01705-2 |
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