BST-236

Abstract

e18520 Background: Cytarabine, the first-line treatment for acute myeloid leukemia (AML), is associated with severe toxicity and high treatment-related mortality (TRM), especially in older patients. Hence, while AML incidence increases with age, advanced age and comorbidities limit cytarabine administration. BST-236 is a new cytarabine pro-drug, enabling delivery of high dose cytarabine to leukemia cells with lower systemic exposure to the free drug. The aim of this study was to evaluate the safety and optimal BST-236 dose in acute leukemia patients. Methods: A Phase I/IIa prospective open label study enrolled adult relapsed/refractory or newly-diagnosed acute leukemia patients. Patients are enrolled into 6 BST-236 escalating-dose cohorts (0.3 – 6 g/m2/d). Treatment was administered as 1-hour daily infusion for 6 days. To date, 18 patients, median age 77 (27-90), were treated with up to 4.5 g/m2/day: 6 relapsed/refractory AML patients, median age 64 (27-81), and 12 newly-diagnosed, unfit for standard chemotherapy patients (7 secondary AML; 5 de novo AML/ALL), median age 79 (70-90). Results: BST-236 treatment was well-tolerated. Only 6 SAEs were assessed as possibly/probably related to BST-236, all “on-target” hematological toxicity events or bacterial infections. The 8-weeks TRM (including from disease progression) in the newly-diagnosed population was 16%. No neurological events or > grade 2 typical cytarabine events such as mucositis, diarrhea, or alopecia were reported during treatment or within 30 days of follow up. Response to the treatment was observed in 6 of the 12 newly-diagnosed patients, including 4 complete remissions (CR), with increased overall survival (OS). No response was reached in the relapse/refractory patients. Conclusions: BST-236 is safe and very well tolerated, enabling delivery of high dose cytarabine to old patients, resulting in overall response and CR rates of 50% and 33%, respectively and increased OS. Notably, 67% of the responding patients had secondary AML, refractory to hypomethylating agents. A phase II study is planned to confirm these encouraging results. Clinical trial information: NCT02544438.