Enter your keyword

Developing Innovative Therapeutic Approaches To Treat Cancer

OXi4503

OXi4503 (combretastatin A1-diphosphate or CA1P) is a dual-mechanism vascular disrupting agent (VDA) that is being developed for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Like its structural analog, CA4P (combretastatin A4-phosphate or fosbretabulin), OXi4503 has been observed to compromise the tumor vasculature, resulting in extensive tumor cell death and necrosis while also possibly affecting the cell shape and attachment of hematopoietic stem cells. In addition, once administered via infusion, it forms a highly reactive orthoquinone metabolite, which has been shown in preclinical studies to have antitumor activity. In preclinical studies, OXi4503 demonstrated potent activity in mice that were carriers of the high-risk subtype FLT3 of human AML. These data have been published in the journal Blood.

OXi4503 was studied in an investigator-sponsored Phase 1 study for the treatment of patients with AML or MDS. The open-label, dose-escalating study was sponsored in part by The Leukemia & Lymphoma Society’s Therapy Acceleration Program, and was conducted by researchers at the University of Florida. The study evaluated the safety profile, maximum tolerated dose (MTD), and biologic activity of OXi4503 in patients with relapsed or refractory AML or MDS. Adverse events attributable to OXi4503 infusion included bone pain, fever, anemia, and thrombocytopenia. Hypertension was manageable and plasma LDH and uric acid increased by at least 2-fold within hours after OXi4503 infusions, suggesting leukemia cell destruction. Clinical data from this Phase 1 study were presented in December 2013 at the 55th American Society of Hematology Annual Meeting and Exposition in New Orleans, Louisiana. Results from 11 patients showed that OXi4503 was generally well tolerated with preliminary evidence of disease response (one patient achieved a marrow complete remission).

OXi4503 is currently being investigated in combination with cytarabine in a Phase 1b/2 study for the treatment of patients with AML or MDS. For more information, please go to clinicaltrials.gov.