View Presentation: Randomized Phase 2 Study to Assess Safety And Efficacy of Low-Dose (LD) Oral Decitabine/Cedazuridine (ASTX727) in Lower-Risk Myelodysplastic Syndromes (LR-MDS) Patients: Interim Safety Analysis
Background and Aims: Cedazuridine (CED), a cytidine deaminase(CDA) inhibitor allows oral availability of decitabine(DEC) and 5 daily doses of the fixed-dose combination of 35 mg DEC/100 mg CED (SD) provides equivalent exposure to an IV DEC regimen of 20 mg/m2 days 1-5 (Garcia-Manero et al, 2020). Attenuated HMA regimens (e.g. 3 days of IV DEC) have shown activity in LR-MDS (Jabbour, et al. 2017). A Phase 1 study of multiple regimens tested in LR-MDS showed 10 mg DEC/100 mg CED D1-5 every 28 days has pharmacodynamic and clinical activity while avoiding severe neutropenia. This study compares this LD regimen to dosing SD at 3 days every 28-days has pharmacodynamic and clinical activity while avoiding severe neutropenia. This study compares this LD regimen to dosing SD at 3 days ever 28-days.
Methods: 81 LR-MDS (IPSS low risk and lnt-1) were randomized to receive 10mg DEC/100 mg CED for 5 days (LD)(n=40) or 35 mg DEC/ 100 mg CED daily for 3 days (SD)(n=41). Study endpoints include clinical activity based on International Working Group (IWG) 2006 MDS response criteria and transfusion independence, leukemia-free survival (LFS), and overall survival (OS) and safety analysis.
Results: Interim safety and treatment discontinuations are presented. Several subjects in both arms discontinued treatment due to BM transplant (~10 subjects). The median duration of exposure was 4-4.5 cycles, and 45% of subjects receiving 3 cycles or less treatment (at ~ 2 months after Last Patient In). Subjects receiving LD had reduced neutropenia compared to those treated with SD.
Conclusion: Overall, Phase 2 study suggests that the LD regimen produces less neutropenia with potential impact on sequelae such as infection.