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

• Published in: Cancer communications (London, England) Vol. 41; no. 2; pp. 171 - 182
• Main Authors: Hong, Ruoxi, Xia, Wen, Wang, Liye, Lee, Kaping, Lu, Qianyi, Jiang, Kuikui, Li, Shengfeng, Yu, Jinquan, Wei, Jin, Tang, Weijia, Zhou, Danyang, An, Xin, Huang, Jiajia, Xue, Cong, Bi, Xiwen, Shi, Yanxia, Yuan, Zhongyu, Xu, Fei, Wang, Shusen
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2021; John Wiley and Sons Inc; Wiley
• Subjects: Antibodies; antibody‐drug conjugate; BAT8001; Breast cancer; Clinical outcomes; Clinical trials; dose escalation; Drug dosages; Ejection fraction; Electrocardiography; Epidermal growth factor; Gene amplification; Hematology; HER2‐postive; Jargon; maximum tolerated dose; Metastasis; Original; Patients; Pharmacokinetics; Toxicity; Tumors; United States > US; dose escalation; breast cancer; HER2-postive; antibody-drug conjugate; maximum tolerated dose; BAT8001
• ISSN: 2523-3548; 2523-3548
• DOI: 10.1002/cac2.12135

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. BAT8001 demonstrated favorable safety and tolerability profiles, with promising anti‐tumour activity in patients with HER2‐positive advanced or recurrent solid tumours. BAT8001 has the potential to provide a new therapeutic option in heavily pretreated patients with metastatic Her2‐positive breast cancer.