Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study

Cancer Communications

article

Ruoxi Hong¹  Weijia Tang³  Danyang Zhou¹  Xin An¹  Jiajia Huang¹  Cong Xue¹  Xiwen Bi¹  Yanxia Shi¹  Zhongyu Yuan¹  Fei Xu¹  Shusen Wang¹  Wen Xia¹  Liye Wang¹  Kaping Lee¹  Qianyi Lu¹  Kuikui Jiang¹  Shengfeng Li³  Jinquan Yu³  Jin Wei⁴ 

[1] Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine;These authors contributed equally to this work.;Biology Research Department, Ltd.;Clinical Development Department, Ltd.

关键词: BAT8001;    antibody-drug conjugate;    HER2-postive;    breast cancer;    dose escalation;    maximum tolerated dose;   

DOI  :  10.1002/cac2.12135

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

Background The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer. Methods This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective. Results Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients. Conclusions BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.

【 授权许可】

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