{"doi":"10.1186/s13045-025-01705-2","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","abstract":null,"journal":"Journal of Hematology & Oncology","year":2025,"id":638640,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":137909,"name":"Jordi Rodon","orcid":null,"position":1,"is_corresponding":false},{"id":1460805,"name":"Yan Liang","orcid":"0000-0003-4029-1765","position":2,"is_corresponding":false},{"id":1658927,"name":"Xinhong Wu","orcid":null,"position":3,"is_corresponding":false},{"id":437695,"name":"Qun Li","orcid":"0000-0002-4734-712X","position":4,"is_corresponding":false},{"id":1658928,"name":"Lihua Song","orcid":null,"position":5,"is_corresponding":false},{"id":169204,"name":"Min Yan","orcid":null,"position":6,"is_corresponding":false},{"id":1658929,"name":"Zhongsheng Tong","orcid":null,"position":7,"is_corresponding":false},{"id":1658930,"name":"YunPeng Liu","orcid":null,"position":8,"is_corresponding":false},{"id":226651,"name":"Zev A. 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Akala","orcid":null,"position":26,"is_corresponding":false},{"id":1658934,"name":"Yongmei Yin","orcid":null,"position":27,"is_corresponding":false},{"id":1658926,"name":"Quchang Ouyang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"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","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. 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