Abstract P5-03-03: Designing a novel platinum chemotherapeutic (IO-125) for treatment of breast cancer

Abstract Triple-negative breast cancer (TNBC) is an aggressive form of cancer occurring in 15-20% of breast cancer patients, with most patients relapsing on currently approved therapy. Recent studies have shown activity of platinum chemotherapy in this class of patients. IO-125 is a novel platinum (II) chemotherapeutic agent with an unique coordination environment. In this study, we investigated the anti-tumor activity of IO-125 in pre-clinical models of TNBC. The coordination environment in IO-125 facilitates supramolecular assembly and releases diaminocyclohexane (DACH)-platinum in a sustained pH-dependent manner. In vitro cell viability studies using an array of breast cancer cell lines shows IO-125 exerts increased potency compared to carboplatin or oxaliplatin. The maximum tolerated (platinum-equivalent) dose (MTD) of IO-125 in mice was 8-fold higher than the MTD (platinum-equivalent) dose of oxaliplatin. The biodistribution and pharmacokinetic profile of IO-125 in plasma and tumor revealed preferential tumor accumulation, significantly increased area-under-the-curve (AUC), a reduction in clearance (CL) and a longer terminal half-life (42 hours) in comparison to oxaliplatin (18 hours). In addition, DNA-Pt adduct formation in tumors was significantly higher for IO-125. When administered at their respective MTDs, IO-125 led to sustained regression of the tumor in a 4T1 syngeneic breast cancer model. Based on these observations, we conclude that IO-125 may emerge as a novel therapeutic against triple negative breast cancer. Citation Format: Sengupta A, Roy M, Sarkar A, Mylavarapu S, Modi S, Gupta N, B H, Hossain S, Ansari A, Pandey M, Yadav Y, Sengupta S. Designing a novel platinum chemotherapeutic (IO-125) for treatment of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-03-03.