Abstract P001: The anti-angiogenic antibody BD0801 demonstrates better anti-tumor activity than bevacizumab and synergize with chemotherapies in multiple tumor models

Abstract

Abstract Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) play a fundamental role in tumor growth and angiogenesis. An increasing number of evidences have suggested enhanced anti-tumor activity when combining anti-angiogenic agents with chemotherapies in the clinic. To support the clinical development of BD0801, a humanized rabbit anti-VEGF monoclonal antibody, we assessed anti-tumor activities of BD0801 using a series of preclinical tumor mouse models including human ovarian cancer OVCAR-8 and SK-OV-3, human non-small cell lung cancer (NSCLC) NCI-H460, and human renal cancer Caki-1 models, with bevacizumab being used as a benchmark. We also investigated the pharmacological kinetics (PK) of BD0801 in cynomolgus monkeys. BD0801 or bevacizumab were intravenously injected into tumor bearing mice at 0.8 mg/kg, 2.5 mg/kg or 7.5 mg/kg twice a week. Combinations of chemotherapy and BD0801 or bevacizumab were also investigated in some of the tumor models. BD0801 presented more potent anti-tumor activities than bevacizumab in ovarian cancer, NSCLC and renal cancer mouse models in a dose-dependent manner. The tumor growth inhibition of BD0801 was 2-20%, 34-66%, or 32-84% when dosed at 0.8 mg/kg, 2.5 mg/kg or 7.5 mg/kg, respectively. Besides, combination of 2.5 mg/kg BD0801 and 10 mg/kg paclitaxel presented a statistically stronger antitumor activity in human ovarian cancer models compared to both single treatments (P<0.05). Combination of 2.5 mg/kg BD0801, 10 mg/kg paclitaxel, and 80 mg/kg carboplatin also presented a stronger antitumor activity than BD0801 or chemotherapy alone in the human NSCLC model. In cynomolgus monkeys received a single intravenous injection of BD0801 at 1.5, 5, and 15 mg/kg, the half-life (t1/2) of BD0801 was 39.4-142 h, the clearance (Cl) was 0.321-0.900 mL/h/kg, and the apparent volume of distribution (Vd) was 49.5-64.4 mL/kg. The peak concentrations (Cmax) of BD0801 were proportional to the doses administered. No difference on the PK parameters was observed between female and male monkeys. Taken together, this study has demonstrated BD0801 as a more potent molecule than bevacizumab in some preclinical tumor models, supporting further clinical development plans for BD0801, especially in combination with chemotherapeutics. Citation Format: Liting Xue, Jianxing Tang, Yuyin Ding, Lei Song, Shansen Xu, Yue Huang, Yan Wu, Wenjie Song, Renhong Tang, Wenqing Yang. The anti-angiogenic antibody BD0801 demonstrates better anti-tumor activity than bevacizumab and synergize with chemotherapies in multiple tumor models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P001.