Abstract
In early trials, 14- and 21-day (d) dosing regimens of oral-AZA were well tolerated and induced hematologic improvement (HI) in patients with lower-risk (LR) MDS. In a Phase III trial, Oral-AZA 300 mg QD for 21d per 28d cycle significantly improved the rate of red blood cell (RBC) transfusion independence (TI) and induced durable HI versus placebo in patients with LR-MDS, although grade 3/4 cytopenias were common in the Oral-AZA arm. These findings support further evaluation of Oral-AZA in MDS.
Evaluate safety and efficacy of the 14d Oral-AZA regimen in patients with low- or intermediate-risk MDS.
An ongoing, multicenter, randomized, Phase II/III trial (CA055-026; NCT05469737).
Adults with International Prognostic Scoring System Revised (IPSS-R)-defined low- or intermediate-risk MDS, Eastern Cooperative Oncology Group performance status ≤2, and ≥1 cytopenia (anemia, thrombocytopenia, or neutropenia), excluding patients with an absolute neutrophil count <0.5 × 109/L ≤1 week of randomization.
Phase II will enroll and randomize ~42 patients 1:1 to receive Oral-AZA 200 or 300 mg QD for 14d per 28d cycle, plus best supportive care (BSC), to determine the recommended Phase III dose. Phase III will enroll and randomize ~188 additional patients 1:1 to Oral-AZA at recommended Phase III dose or placebo for 14d per 28d cycle, plus BSC. Patients in the placebo arm with stable disease at Cycle 6 or disease progression after ≥3 cycles may opt to cross over into the Oral-AZA arm. Patients benefitting from Oral-AZA may continue treatment in an extension phase.
Phase II primary endpoints are safety and complete remission (CR) rate in ≤6 treatment cycles. Secondary endpoints are overall response rate (ORR), packed RBC-TI and platelet-TI sustained for 84d in ≤6 cycles. ORR includes CR, partial remission, marrow CR, and HI. Phase III primary endpoint is CR in ≤6 treatment cycles and key secondary endpoint is 84d packed RBC-TI. Other secondary endpoints include those in Phase II, plus overall survival, event-free survival, time to AML progression, iron parameters, health-related quality of life, healthcare resource utilization, and safety parameters.
Recruitment began December 2022 and is ongoing.
EHA2023 Congress.