Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies.
Publication Title
J Hematol Oncol
Document Type
Article
Publication Date
6-6-2025
Keywords
Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Antibodies, Bispecific; Antibodies, Monoclonal, Humanized; Immunoconjugates; Maximum Tolerated Dose; Neoplasm Metastasis; Neoplasms; Triple Negative Breast Neoplasms; Camptothecin; Antibody–drug conjugate; HR+/HER2− breast cancer; Sac-TMT; Triple-negative breast cancer.; oregon; chiles
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.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Hematology
DOI
10.1186/s13045-025-01705-2.
