On 7th June 2017, the U.S. Food and Drug Administration (FDA) granted a Fast Track Designation to OXi4503 for the treatment of patients with Acute Myeloid Leukemia (AML).1
OXi4503 (combretastatin A1 di-phosphate) is a dual mechanism vascular disrupting agent that has been shown to destroy tumor vasculature, leading to extensive tumor cell death and necrosis. Additionally, OXi4503 can undergo oxidative stress to quinone intermediate to produce cytotoxicity against tumor cells. Preclinical studies of OXi4503 in AML have shown that this agent could induce phenotypic and molecular remissions in subtypes of AML including Fms Like Tyrosine Kinase 3 (FLT3) mutated AML through multiple mechanisms including vascular disruption and apoptosis. 2
OXi4503 is currently being explored in a phase I/II study (NCT02576301) in patients with Relapsed or Refractory (R/R) AML. The aim of the phase 1 portion of this study is to investigate the maximum tolerated dose of OXi4503 monotherapy and in combination with intermediate-dose cytarabine in R/R AML patients. The aim of the phase II portion of the study is to investigate the overall response rate of OXi4503 in combination with intermediate-dose cytarabine in R/R AML patients after treatment failure of up to 1 prior chemotherapy regimen.