Abstract P1-18-36: The safety, tolerability, and pharmacokinetics of BAT8001 in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer: An open-label, dose-up, phase 1 study
Authors: Wang Shusen , Hong Ruoxi , Wang Liye , Xu Fei , Xia Wen 
Published: March 2020

Abstract
Background BAT8001 for injection is a novel antibody-drug conjugate (ADC) that targets HER2, which is composed of trastuzumab analogue (BAT0606) covalently linked to the drug-linker Batansine (a derivative of maytansine, which refers to the 3AA-MDC complex) by a stable thioether bond. Patients and methods In this open-label, phase 1 trial, we recruited 29 patients aged 18 years or older with HER2-positive advanced or recurrent breast cancer who had been previously treated with trastuzumab and/or lapatinib plus cytotoxic agents. Criteria for eligibility included HER2-positivity, having evaluable lesions as defined per Response Evaluation Criteria in Solid Tumors, version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received BAT8001 intravenously once every 21 days, with dose escalation in five cohorts: 1.2mg/kg, 2.4mg/kg, 3.6mg/kg, 4.8mg/kg, and 6.0mg/kg. This study used a modified 3 + 3 dose escalation design to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. Analyses included all patients who had received at least one dose of study treatment. The primary objective was to establish the safety, tolerability, pharmacokinetics (PKs), immunogenicity of BAT8001 in patients with HER2-positive metastatic breast cancer. The secondary objectives included evaluation of the metabolites and to make a preliminary assessment of the efficacy of BAT8001 for HER2 positive advanced solid tumors. Results Twenty-nine patients were enrolled in this study. The dose-limiting toxicity was grade 4 thrombocytopenia, which occurred in two patients administered of 6.0mg/kg, two patients administered of 4.8mg/kg and one patient administered of 3.6mg/kg BAT8001; thus, the maximum tolerated dose was 3.6mg/kg. The most common adverse event (AE) for any grade was increased aspartate aminotransferase, increased alanine aminotransferase, thrombocytopenia, increased alkaline phosphatase, increased uric acid, neutropenia, diarrhoea, nausea, vomiting, fatigue, and anemia. Grade 3 or greater AE occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhoea in 2 (6.9%) patients, and anemia in 1 (3.4%) patients. Objective responses (all partial responses) were observed in 11 (37.9%) and disease control rate in 24 (82.8%) of 29 patients who were evaluable for anti-tumor activity. The objective response rate and the disease control rate confirmed after 4 weeks was 27.6% and 65.5%, respectively. No pharmacokinetic interaction was observed. The total antibodies of BAT8001 were linearly correlated with the dose range of 1.2 to 6 mg/kg. Conclusions BAT8001 was safe, tolerable and the preliminary activity seems promising in patients with HER2-positive advanced or recurrent breast cancer. The results suggest that BAT8001 has the potential to provide a new therapeutic option in heavily pretreated patients with metastatic breast cancer.
Citation Format: Shusen Wang, Ruoxi Hong, Liye Wang, Fei Xu, Wen Xia. The safety, tolerability, and pharmacokinetics of BAT8001 in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer: An open-label, dose-up, phase 1 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-36.