Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies
机构：[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江苏省人民医院[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.河南省肿瘤医院[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.中山大学附属第二医院[12]The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.河北医科大学第四医院[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.
BackgroundSacituzumab 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).MethodsPatients 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.ResultsThirty 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).ConclusionsSac-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 registrationClinicalTrials.gov, NCT04152499.
基金：
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA - MSD
Ouyang Quchang,Rodon Jordi,Liang Yan,et al.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].JOURNAL OF HEMATOLOGY & ONCOLOGY.2025,18(1):doi:10.1186/s13045-025-01705-2.
APA：
Ouyang, Quchang,Rodon, Jordi,Liang, Yan,Wu, Xinhong,Li, Qun...&Yin, Yongmei.(2025).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,18,(1)
MLA：
Ouyang, Quchang,et al."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 18..1(2025)
医学