The phase II ASTX727-10 study evaluating the combination of a hypomethylating agent (HMA) plus magrolimab in patients with intermediate to very high-risk myelodysplastic syndromes (MDS) has begun enrollment, according to a poster presentation at the Eleventh Annual Meeting of the Society of Hematologic Oncology.
Amer Zeidan, MBBS, MHS, of Yale University, and colleagues are conducting the study to assess if using oral decitabine/cedazuridine in combination with magrolimab may “provide the benefits of combination therapy without the significant burden of parenteral therapy.”
Phase II ASTX727-10 Eligibility Criteria, Design
The primary aim of the phase II study is to evaluate the safety and efficacy of the combination treatment in patients who have intermediate to very high-risk MDS per the MDS International Prognostic Scoring System – Revised (IPSS-R). The secondary aims of the study include evaluating the pharmacokinetic profiles of oral decitabine/cedazuridine and magrolimab, other clinical efficacy data on the combination, and safety and efficacy in prespecified subgroups of patients.
Dr. Zeidan and colleagues began enrolling patients in April 2023. To be eligible for the single-arm, open-label study, patients must meet certain criteria. Patients must have previously untreated MDS with <20% bone marrow blasts, as well as an Eastern Cooperative Oncology Group Performance Status ≤2, and be willing to undergo red blood cell transfusions to achieve a hemoglobin >9 gm/dl at the start of study treatment, “per protocol parameters, and as clinically necessary,” according to Dr. Zeidan and colleagues.
Key exclusion criteria include “significant medical issues,” creatinine clearance < 50 ml/min, immediate eligibility for hematopoietic stem cell transplant, secondary MDS, or MDS/myeloproliferative neoplasm overlap syndromes, the researchers wrote.
“Tolerability of the combination regimen will be confirmed in the first six to 18 subjects with dose and/or dosing decreases identified during this assessment applied to the entire study,” Dr. Zedian and colleagues wrote.
Zeidan A, Mosher K, Souza S, et al. Phase 2 study of oral decitabine/cedazuridine in combination with magrolimab for previously untreated subjects with intermediate to very high-risk myelodysplastic syndromes (MDS). Abstract MDS 622. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.