A multi-centre, phase 1a/1b dose escalation and expansion study of the HER2-directed antibody–drug conjugate T-Bren (BL-M07D1) in advanced breast cancer and other solid tumours
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Trastuzumab brengitecan (T-Bren; BL-M07D1) is a HER2-directed antibody-drug conjugate (ADC) comprising a monoclonal antibody, a cathepsin B-cleavable linker, and a potent topoisomerase I inhibitor payload (Ed-04). We aimed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumour activity of T-Bren in patients with advanced breast cancer and other solid tumours. METHODS: This phase 1 dose escalation and expansion study enrolled patients with inoperable locally advanced or metastatic breast cancer or other solid tumours pretreated with systemic therapy. Patients received intravenous T-Bren at doses ranging from 1.0 mg/kg on days 1 and 8 every 3 weeks (D1D8 Q3W) (accelerated titration), to 2.6 mg/kg, 3.2 mg/kg, 3.8 mg/kg, 4.4 mg/kg, 5.0 mg/kg, 5.6 mg/kg, 6.2 mg/kg on day 1 every 3 weeks (D1Q3W) (i3+3 design). Primary objectives were to assess dose-limiting toxicity/maximum tolerated dose (DLT/MTD), and establish the recommended phase 2 dose (RP2D). FINDINGS: Overall, 253 patients were treated: DLTs occurred in two patients treated at 6.2 mg/kg Q3W, including grade 4 neutropenia with myelosuppression and grade 3 thrombocytopaenia in one patient, and grade 4 febrile neutropenia in another. In patients with breast cancer, ORR was 81.5% (66/81) in HER2-positive subgroup, 69.5% (57/82) in hormone receptor-positive/HER2-low disease, and 58.3% (14/24) in hormone receptor-negative/HER2-low disease. Median PFS was 18.2 months, 14.0 months, and 7.2 months in the HER2-positive, HR-positive/HER2-negative, and HR-negative/HER2-negative subgroups, respectively. INTERPRETATION: T-Bren demonstrated a manageable safety profile and clinically meaningful antitumour activity across a broad spectrum of HER2 expression in advanced breast cancer. The 4.4 mg/kg every three weeks regimen was established as the RP2D in breast cancer. FUNDING: This study was funded by the sponsor Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Source: EBioMedicine
Institutions: Sun Yat-sen University, Sun Yat-sen Memorial Hospital, First Affiliated Hospital of Zhengzhou University, Jinan Central Hospital, Shandong First Medical University, Dongguan People’s Hospital, Southern Medical University, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Hospital, Sir Run Run Shaw Hospital, Zhejiang University, Zhongnan Hospital of Wuhan University, Sichuan University, West China Hospital of Sichuan University, Anyang Tumor Hospital, Shanxi Provincial Cancer Hospital, Xuzhou Central Hospital, Southeast University, Sichuan Baili Pharmaceutical Co., Ltd. (China), Fujian Medical University, Fujian Provincial Cancer Hospital
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
OpenAlex ID: W7165864111