Abstract 4796: BTK inhibitor BGB-3111 synergizes with lenalidomide in MCL models

Background BGB-3111 is a novel, irreversible, second generation BTK inhibitor with better selectivity profile and DMPK property compared to ibrutinib. It has demonstrated promising anti-tumor activities in patients with advanced B cell malignancies, including mantle cell lymphoma (MCL). Lenalidomide is an immunomodulatory agent with single-agent activity in several histologic subtypes of B-cell non-Hodgkin lymphoma (NHL). It was approved for the treatment of patients with MCL whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In this study, we sought to investigate the combination activities of BGB-3111 and lenalidomide in MCL models. Methods In vitro drug efficacy was determined using MCL cell lines including REC-1, MINO and JEKO-1. Cell viability was assessed with Cell Titer Glo® assay and half maximal inhibitory concentrations (IC50) were estimated upon exposure to single agents or drug combinations. In vivo activity was assessed in REC-1 and MINO subcutaneous mouse xenograft models. Treatments were administered by oral gavage when tumors were palpable and individual body weight and tumor volume was recorded twice weekly. Results The in vitro combination activity of BGB-3111 and lenalidomide was tested in MCL cell lines. Strong synergy was observed in REC-1 and MINO cells, but not in JEKO-1 cells. When tested in vivo, both BGB-3111 (7.5 mg/kg, BID) and lenalidomide (30 mg/kg, QD) significantly inhibited the REC-1 xenograft tumor growth with TGI of 86% and 56%, respectively. The combination treatment resulted in 100% TGI. In MINO xenograft model, combination treatment of BGB-3111 (30 mg/kg, BID) and lenalidomide (30 mg/kg, QD) was also more efficacious than either single agent. Conclusions In summary, BGB-3111 and lenlidomide showed interesting in vitro and in vivo combination activity in MCL models, providing rationale for testing this combination in clinic. Citation Format: Nan Hu, Shuo Zhang, Min He, Jiye Zhang, Bin Jiang, Zhijian Sun, Lusong Luo, Lai Wang. BTK inhibitor BGB-3111 synergizes with lenalidomide in MCL models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4796.