A Multi-phase, Dose-Escalation Followed by an Open-label, Randomized, Crossover Study of Oral ASTX030 (Cedazuridine and Azacitidine Given in Combination) Versus Subcutaneous Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)

Inclusion Criteria:

1. Confirmed MDS, CMML, MDS/MPN, or AML who are candidates to receive and benefit from single agent azacitidine as follows and as applicable according to local country approvals and/or local institution standard practice:
   1. French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS). MDS/MPN patients including CMML according to the World Health Organization (WHO) 2016 classification are also eligible if they are candidates to receive single agent azacitidine per local institution standards; or
   2. Previously untreated AML with 20% to 30% blasts present in bone marrow and multi-lineage dysplasia (Phase 2 and 3 only); or
   3. Previously untreated AML with >30% blasts present in bone marrow, who are not eligible for stem cell transplant and unfit for intensive chemotherapy induction (Phase 2 and 3 only).
2. Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
3. Participants with adequate organ function defined as:
   1. Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤2.5 × ULN.
   2. Renal: Calculated creatinine clearance >50 mL/min/1.73 m^2 by Cockcroft-Gault formula or other medically acceptable formulas.
4. For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD) and must be ≥2 weeks off systemic immunosuppressive therapy before start of study treatment.
5. Participants with no major surgery within 2 weeks before first study treatment.
6. Participants with no cytotoxic chemotherapy within 4 weeks before first study treatment.
7. Able to swallow the number of tablets/capsules required for the treatment assignment within a 10-minute period and tolerate 4 hours of fasting.
8. Participants with projected life expectancy of at least 12 weeks.
9. 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.

Exclusion Criteria:

1. Active uncontrolled gastric or duodenal ulcer.
2. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled bacterial, viral, or fungal infections.
3. Life-threatening illness (e.g., uncontrolled bleeding and patients at risk for or are experiencing leukostasis [AML]), uncontrolled medical condition or organ system dysfunction, or other reasons, which, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of oral cedazuridine + azacitidine or compromise the integrity of the study outcomes.
4. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the participant has been disease free for at least 2 years.
5. Participants with MDS/MPN who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
6. Previous treatment with more than 1 cycles of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
7. Treated with any investigational drug or therapy within 2 weeks, or 5 half lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
8. Known or suspected hypersensitivity to cedazuridine or azacitidine, or any of their excipients.