Abstract 1551: Identification of plasma biomarker concentration changes resulting from the administration of the Vascular Disrupting Agent BNC105 across 3 clinical trials in mesothelioma, ovarian and renal cancer
Authors: Kremmidiotis Gabriel , Leske Annabel , Simpson Jeremy , Doolin Elizabeth , Iglesias Jose 
Published: August 2015

BNC105 is a tubulin depolymerisation agent. Its activity includes effects on both cancer cells and on solid tumor microvasculature. BNC105 shows evidence of strong anti-cancer efficacy in vitro and in animal models. In solid tumors its efficacy is driven by selective destruction of tumor vasculature (Vascular Disrupting Agent - VDA) and direct action on tumor cells through suppression of their proliferation. In non-proliferating blood cancers (e.g. Chronic Lymphocytic Leukaemia) BNC105 activates pro-apoptotic proteins, which mediate cancer cell death. BNC105P may be useful in the treatment of human cancers both as a monotherapy and also in combination therapies. To date BNC105 has been evaluated in mesothelioma as a monotherapy, in ovarian cancer in combination with gemcitabine/carboplatin and in renal cancer in combination with everolimus. Seventy nine (79) patients receiving intravenous administrations of BNC105 in these trials were blood sampled at baseline and following BNC105 administration. The plasma concentrations of a panel of 83 plasma analytes were investigated for changes resulting from the administration of BNC105. Here, we report data across the three clinical trials on plasma biomarkers that consistently change in response to the administration of BNC105. Our findings include a number of biomarkers that have not been previously associated with the action of a VDA. Significant increases within 3 hours following BNC105 administration were observed across all studies regardless of monotherapy or combination. These included Ferritin, IL-8, IL-10, IL-16, MIP1B, MCP-1, TNFR2, and MMP9. Decreases in several markers were also observed that included Alpha-2 Macroglobulin, Myoglobin, PAI-1, TIMP-1. Correlation of biomarker changes to 6 month Progression free survival (6MPFS) was undertaken in 44 patients treated with BNC105+everolimus in the phase II renal cancer trial. This analysis resulted in the identification of 4 plasma analytes where changes from baseline were associated with progression free survival at 6 months. Taken together, the biomarker program that has accompanied the clinical development of BNC105 has allowed the identification of exploratory plasma biomarkers associated with treatment with a VDA that can potentially identify patient populations that respond better to treatment. These results will support the continued development of BNC105 in biomarker-guided clinical trial designs.

Citation Format: Gabriel Kremmidiotis, Annabel Leske, Jeremy Simpson, Elizabeth Doolin, Jose Iglesias. Identification of plasma biomarker concentration changes resulting from the administration of the Vascular Disrupting Agent BNC105 across 3 clinical trials in mesothelioma, ovarian and renal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1551. doi:10.1158/1538-7445.AM2015-1551