Abstract CT189: A phase I study of BAT1006, a novel anti-HER2 antibody, in patients with locally advanced/metastatic solid tumors

Abstract Purpose: BAT1006 is a HER2 extracellular domain II-targeted monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) effect aiming for Her2-positive locally advanced/metastatic solid tumors. Previous studies have shown that de-fucosylated antibody binds to FcγRIIIa with increased affinity and can thus trigger FcγRIIIa-mediated effector functions more efficiently than native antibody. BAT1006 was expressed in an FUT8-knockout CHO cell line, resulting in antibody completely devoid of fucose modification. With approximate 5-fold higher level of ADCC effect compared to Pertuzumab, BAT1006 also exhibited potent anti-tumor activity in HER2 positive Calu-3 xenograft mice model. The ongoing phase I, open-label, first-in-human study is evaluating the safety, pharmacokinetics (PK), immunogenicity and preliminary efficacy of BAT1006 to determine the Maximum-Tolerated Dose (MTD) and/or recommended phase II dose (RP2D). Methods: Patients with locally advanced/metastatic solid tumors received escalating doses of BAT1006 (3, 6, 10, 15 mg/kg), administered intravenously (IV) once every three weeks. Patients must have had documented HER2 positivity defined as 3+ by validated immunohistochemistry or amplified on in situ hybridization (ISH). Assessments include archival tumor molecular status, PK, and efficacy by Response Evaluation Criteria in Solid Tumors (RECIST). Results: Fifteen patients [with 2-9 prior lines of therapy] have been treated with BAT1006. All patients had metastatic breast cancer and had received previous HER2-targeted therapies including Trastuzumab, Pertuzumab, T-DM1 and Pyrotinib. No treatment related ≥ Grade 3 AEs have been observed. Of 9 patients at 10mg/kg and 15mg/kg, 1 in 3 patients had CR at 10mg/kg, 2 in 6 patients had PR at 15mg/kg. Conclusion: BAT1006 was well tolerated and showed promising anti-tumor activity in patients with heavily pre-treated HER2-positive cancers. Based on the safety and efficacy results, one additional dose level (20 mg/kg) will be added to the escalation phase and combination therapy with other HER2-based therapy will also be initiated. Citation Format: Xingxing Mei, Weijia Tang, Shuqiang Song, Hao Wang, Chuanqi Cao, Cuiying Feng, Bert E. Thomas, Shengfeng Li, Jin-Chen Yu. A phase I study of BAT1006, a novel anti-HER2 antibody, in patients with locally advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT189.