Inclusion Criteria for the Main Extension Study:

Participants must fulfill all of the following inclusion criteria:

1. Previous participation in an Astex-sponsored ASTX727 clinical trial (including, but
not limited to studies ASTX727-01, ASTX727-02, and ASTX727-04) in which the
participant was treated with ASTX727 and was still on active treatment with ASTX727 at
the time of study completion as determined by Astex.

2. Participant is considered to be benefitting from ASTX727 treatment in the opinion of
the treating investigator at the time of parent study completion (Participants must
not be withdrawn from the parent study until eligibility for this study is confirmed).

3. Participant is able to understand and comply with the study procedures and understands
the risks involved in the study.

4. Participant provides legally effective informed consent before undergoing any
study-specific procedure.

5. Women of childbearing potential must not be pregnant or breastfeeding and must have a
negative pregnancy test at screening. Women of childbearing potential must agree to
practice 2 highly effective contraceptive methods of birth control and must agree not
to become pregnant for 6 months after completing treatment; men with female partners
of childbearing potential must agree to practice 2 highly effective contraceptive
measures and must agree not to father a child while receiving ASTX727 and for at least
3 months after completing ASTX727 treatment.

Inclusion Criteria for the Food Effect Substudy:

1. Participants must have a confirmed diagnosis of-

i. 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, CMML), and participants with MDS
International Prognostic Scoring System (IPSS) int-1, -2, or high-risk MD.

ii. AML, as diagnosed according to the 2016 World Health Organization (WHO) guidelines
on acute leukemia, of any subtype except M3 (acute promyelocytic leukemia), who are
not candidates for intensive chemotherapy, including participants receiving
hypomethylating agent (HMA) treatment, who have a confirmed diagnosis and a prior
confirmatory bone marrow report. Participants who are currently receiving HMA
treatment must complete the ongoing (at the time of Screening) treatment cycle before
enrolling in this study; timing of start of treatment cycle with ASTX727 is at the
principal investigator's discretion.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

3. Adequate organ function defined as follows:

1. Hepatic: Total bilirubin ≤1.5 × 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: Calculated creatinine clearance ≥60 mL/min.

Exclusion Criterion for the Main Extension Study:

1. Any participant who, in the opinion of the investigator, may have other conditions,
organ dysfunction, or for whom safety data from parent study participation suggests the
risks of continuing treatment with ASTX727 may outweigh the benefits.

Exclusion Criteria for the Food Effect Substudy:

1. Participants with known or suspected hypersensitivity to decitabine, cedazuridine, or
any of the excipients in the ASTX727 tablets.

2. Poor medical risk because of other conditions such as uncontrolled systemic diseases
or active uncontrolled infections.

3. Life-threatening illness, medical condition or organ system dysfunction, or other
reasons including laboratory abnormalities, which, in the Investigator's opinion,
could compromise the participant's safety, interfere with the absorption or metabolism
of decitabine + cedazuridine or compromise the integrity of the study outcomes.

4. Prior gastric surgery for ulcer disease, weight loss, etc, that would impair normal
motility or absorption.

5. Second malignancy currently requiring active chemotherapy. To clarify, participants
with breast or prostate cancer stable on or responding to endocrine therapy, are
eligible.

6. Known history of human immunodeficiency virus or known seropositive for hepatitis C
virus or hepatitis B virus.

7. Active uncontrolled gastric or duodenal ulcer.

8. Participants with acute promyelocytic leukemia.

9. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white
blood cell (WBC) counts.

10. 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 AEs from previous treatment with
investigational drug or therapy.