Sunesis Pharmaceuticals, Inc. has announced favorable results from a Washington University-sponsored Phase I trial of vosaroxin plus azacitidine in patients with myelodysplastic syndrome, and from an analysis of the company's Phase III VALOR trial of vosaroxin and cytarabine in relapsed/refractory acute myeloid leukemia, or AML. In a Phase I/II, open label, dose-escalation trial sponsored by the Washington University School of Medicine, patients with MDS who may have received up to three prior cycles of hypomethylating agent-based therapy were given vosaroxin and azacitidine for a maximum of six cycles. The Phase I portion of the study was designed to determine the maximum tolerated dose and dose limiting toxicity of the combination.

Other endpoints include best response, safety, tolerability, and event-free, progression-free, disease-free and overall survival. Thirteen patients were enrolled in the dose-escalation phase and five of twenty planned patients have been enrolled in the expansion cohort to date. At the initial dose of 50 mg/m2/day vosaroxin, 2 of 6 patients experienced a DLT (grade 4 hyperbilirubinemia, and grade 4 neutropenia >42 days).

The vosaroxin dose was de-escalated to 34 mg/m2/day, resulting in 1 of 6 patients with a DLT (grade 4 mucositis). Of the 18 patients enrolled to date, 16 completed greater than or equal to 1 cycle and are evaluable for response. Best response for each patient was as follows: stable disease, n=3; stable disease with hematologic improvement (HI)-neutrophils, n=2; marrow complete remission (CR), n=4; marrow CR with HI-platelets; n=2; marrow CR with HI-neutrophils, n=1; marrow CR with HI-erythroid, n=1; and marrow CR with HI-platelets and neutrophils, n=1; and CR, n=1. One patient had progressive disease (PD).

Of the 16 evaluable patients, 6 have proceeded to allogenic stem cell transplant and 3 are actively undergoing study treatment. The major non-hematologic toxicities of febrile neutropenia, infections, and mucositis were expected based on the disease population and prior experiences with vosaroxin.