Study of ASTX727 vs IV Decitabine in Participants With MDS, CMML, and AML

Summary

Multicenter PK study of ASTX727 versus IV decitabine. Adult participants who were candidates to receive IV decitabine were randomized 1:1 to receive the ASTX727 tablet Daily×5 in Cycle 1 followed by IV decitabine 20 mg/m\^2 Daily×5 in Cycle 2, or the converse order. After completion of PK studies during the first 2 treatment cycles, participants continued to receive treatment with ASTX727 from Cycle 3 onward (in 28-day cycles) until disease progression, unacceptable toxicity, or the participants discontinued treatment or withdrew from the study.

Timeline

Start

2018-02-15

Primary completion

2021-09-10

Completion

2023-05-25

Outcome

Met primary endpoint

paper Primary endpoint of total exposure of oral decitabine-cedazuridine versus intravenous decitabine was 98·93% (90% CI 92·66-105·60), indicating equivalent pharmacokinetic exposure on the basis of area under the curve. PMID 38135371 ↗

release “The data demonstrated that the ASCERTAIN study met the primary endpoint of total 5-Day decitabine Area-Under-The-Curve (AUC) equivalence of oral C-DEC and IV decitabine.” taihooncology.com ↗

release “The ASCERTAIN study met its primary endpoint” otsuka.co.jp ↗

release “The ASCERTAIN study met its primary endpoint, with the orally administered decitabine and cedazuridine fixed-dose combination showing pharmacokinetic exposure equivalence” otsuka.co.jp ↗

Publications

• Garcia-Manero G, McCloskey J, Griffiths EA, Yee KWL, Zeidan AM, Al-Kali A, Deeg HJ, Patel PA, Sabloff M, Keating MM, Zhu N, Gabrail NY, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern AE, O'Connell CL, Roboz GJ, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao KH, Oganesian A, Hao Y, Keer HN, Azab M, Savona MR. Oral decitabine-cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. Lancet Haematol. 2024 Jan;11(1):e15-e26. doi: 10.1016/S2352-3026(23)00338-1.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	ASTX727	Unknown	—	Oral
Subject	Decitabine	Small molecule	20 mg/m2	Intravenous

Indications