Abstract 5458: Pharmacodynamics of WX-0593 combined with bevacizumab biosimilar on human lung cancer xenograft mouse models

Abstract

Abstract Objective: To evaluate the antitumor activity of WX-0593 (anaplastic lymphoma kinase/ROS proto-oncogene 1 receptor tyrosine kinase [ALK/ROS1] tyrosine kinase inhibitor) combined with bevacizumab biosimilar in vivo. Methods: Cell line-derived xenograft (CDX) model: NCI-H3122 cell suspension was subcutaneously inoculated into the right axilla of BALB/c-nu mice. When the average tumor volume reached 100-300 mm3, the mice were randomly divided into six groups (eight mice/group) and administered with solvent, WX-0593 1.5 or 5 mg/kg, bevacizumab biosimilar 1 mg/kg, or WX-0593 1.5 or 5 mg/kg + bevacizumab biosimilar 1 mg/kg, respectively. Patient-derived xenografts (PDX) model: LU-01-1443 tumor tissue blocks of 20-30 mm3 were subcutaneously inoculated into the right axilla of BALB/c-nu mice. When the average tumor volume reached 115 mm3, the mice were randomly divided into four groups (eight mice/group) and administered with solvent, WX-0593 2.5 mg/kg, bevacizumab biosimilar 1.5 mg/kg or their combination. Tumor diameter was measured twice a week. The tolerability was also assessed. Results: CDX tumor model: There were significant differences between each group and the control group (all P <0.01). The combination of WX-0593 5 mg/kg and bevacizumab biosimilar 1 mg/kg was significantly more effective than WX-0593 5 mg/kg alone or bevacizumab biosimilar 1 mg/kg alone (both P <0.01). PDX tumor model: Compared with the control group, single-agent WX-0593 2.5 mg/kg and bevacizumab biosimilar 1.5 mg/kg delayed tumor growth. The tumor suppressive effect of WX-0593 combined with bevacizumab biosimilar was impressive (treated/control ratio =11.81%; tumor growth inhibition =92.19%) and significantly better than WX-0593 2.5 mg/kg or bevacizumab biosimilar 1.5 mg/kg alone (P =0.004, 0.003, respectively). Toxicity: There were no abnormalities in appearance and mental state in each group during the experiment, and the weight of the mice remained stable. Conclusions: The combination of WX-0593 and bevacizumab biosimilar had obvious synergistic effect and showed potent tumor suppressive activity, which was significantly better than WX-0593 or bevacizumab biosimilar alone at the same dose. There was no drug-related toxicity in all groups, and no increase in toxicity after combined administration. Citation Format: Shansong Zheng, Qingmei Zheng, Xin Dong, Xinmei Wang, Dongmei Chen, Huicheng Duan, Cuicui Ma, Chenwei Zhang. Pharmacodynamics of WX-0593 combined with bevacizumab biosimilar on human lung cancer xenograft mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5458.