This study is designed to examine blood levels of ASTX727, a fixed-dose combination tablet
containing the combination of cedazuridine (100 mg) and decitabine (35 mg), when given under
fed versus fasted conditions to participants with myelodysplastic syndromes (MDS), including
refractory anemia with excess blasts in transformation or chronic myelomonocytic leukemia
(CMML). This study will also assess the safety of ASTX727.
This is a Phase 1b, multicenter, open-label, randomized, two-sequence, crossover study of
ASTX727 in participants with MDS, including refractory anemia with excess blasts in
transformation or CMML. Participants will continue to be enrolled until evaluable data is
collected from 12 participants. It is expected that approximately 18 participants will be
enrolled in total.
This study will be conducted in 28-day cycles. All participants will take part in Cycle 1 and
may continue into Cycles ≥2 at the investigator's discretion. Participants will receive one
tablet of ASTX727 containing 100 mg cedazuridine and 35 mg decitabine once daily for 5 days
in 28-day cycles starting from Cycle 1 Day 1.
Participants will be randomized in a 1:1 ratio to receive high-calorie, high-fat breakfast
meal pre-dose on either Day 2 or Day 4 of Cycle 1. Blood will be drawn at specified time
points in Cycle 1 on Days 2 through 5 to assess the effect of food on the PK of cedazuridine
After completion of the first treatment cycle, participants may continue to receive treatment
with ASTX727 at the investigator's discretion for subsequent cycles (Days 1 through 5 of
28-day cycles), until disease progression, unacceptable toxicity, investigator decision to
discontinue treatment, or the participant decides to discontinue treatment or withdraw from
the study. In Cycles ≥2, participants will fast for 2 hours before and 2 hours after taking
the ASTX727 tablet on all dosing days.
1. Able to understand and comply with the study procedures, including the ability to
completely consume the breakfast meal in 20 minutes, understand the risks involved in
the study, and provide written informed consent before the first study-specific
2. Men or women ≥18 years with MDS, including all French-American-British subtypes
(refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with
excess blasts, refractory anemia with excess blasts in transformation, and CMML), and
subjects with MDS int-1, -2, or high-risk MDS.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. Adequate organ function defined as follows:
1. Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate
aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine
aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤5 × ULN.
2. Renal: serum creatinine ≤1.5 × ULN or if serum creatinine is elevated; calculated
creatinine clearance or glomerular filtration rate ≥50 mL/min.
5. Women of child-bearing potential (according to recommendations of the Clinical Trial
Facilitation Group) must not be pregnant or breastfeeding and must have a negative
pregnancy test at screening.
6. Subjects and their partners with reproductive potential must agree to use 2 highly
effective contraceptive measures during the study and must agree not to become
pregnant or father a child for 3 months after the last dose of study treatment.
1. Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine.
2. Treated with any investigational drug or therapy within 2 weeks of study treatment, or
5 half-lives, whichever is longer, before the protocol-defined first dose of study
treatment, or ongoing clinically significant adverse events (AEs) from previous
treatment with investigational drug or therapy.
3. Poor medical risk because of other conditions such as uncontrolled systemic diseases
or active uncontrolled infections.
4. Life-threatening illness, medical condition or organ system dysfunction, or other
reasons including laboratory abnormalities, which, in the investigator's opinion,
could compromise the subject's safety, interfere with the absorption or metabolism of
decitabine + cedazuridine or compromise the integrity of the study outcomes.
5. Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal
motility or absorption.
6. Prior malignancy, except for adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, non-metastatic prostate cancer with normal
prostate-specific antigen, or other cancer from which the subject has been disease
free for at least 3 years.
7. Known history of human immunodeficiency virus or if known seropositive for hepatitis C
virus or hepatitis B virus.
8. Active uncontrolled gastric or duodenal ulcer.