Inclusion Criteria:

        Age

          1. Participant must be 18 years of age or older, at the time of signing the informed
             consent.

             Type of Participant and Disease Characteristics

          2. Have histologically or cytologically confirmed advanced solid tumors that are
             metastatic or unresectable and are refractory or have relapsed after treatment with
             standard available therapies or for whom standard life-prolonging measures are not
             available.

               1. Phase 1: any tumor type is eligible

               2. Phase 2: eligible tumor types as follows: malignant pleural mesothelioma (MPM)
                  (Cohort 1); sarcomas with human murine double minute 2 (MDM2) amplification
                  (Cohort 2); any solid tumors with CDNK2A loss (Cohort 3); any solid tumors with
                  molecular feature that may confer sensitivity to ASTX295 (Cohort 4).

          3. Documented wild-type TP53 gene status.

          4. Have an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 2.

          5. Acceptable bone marrow function, as evidenced by the following laboratory data:

               1. Absolute neutrophil count (ANC) ≥1500 cells/mm3

               2. Platelet count ≥100,000 cells/mm3

               3. Hemoglobin >9 g/dL

          6. Adequate hepatic function as evidenced by:

               1. Serum total bilirubin ≤1.5 × upper limit of normal (ULN).

               2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤
                  3 ULN in the presence of liver metastases).

               3. Serum creatinine ≤1.5 × ULN OR calculated creatinine clearance (by the standard
                  Cockcroft-Gault formula) of ≥50 mL/min or measured glomerular filtration rate of
                  ≥50 mL/min.

             Sex

          7. Participant can be male or female

             Informed Consent

          8. Capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol, and willing to participate in the study.

             Participants are eligible to be included in Phase 1 Part B of the study only if all of
             the following additional criteria apply:

          9. In Phase 1 Part B (dose expansion) of the protocol, subjects must have disease lesions
             that are amenable to biopsy and must agree and be able to undergo a pre- and on-
             treatment biopsy.

             Participants are eligible to be included in Phase 2 of the study only if all of the
             following additional criteria apply:

         10. There is confirmed availability of sufficient tumor specimen either from archival
             formalin-fixed, paraffin embedded (FFPE) tissue or tissue obtained by a fresh biopsy
             for analyzing TP53 at a central laboratory.

         11. Measurable disease according to appropriate criteria as per protocol.

        Exclusion Criteria:

        Medical Conditions

          1. Poor medical risk in the investigator's opinion because of systemic diseases in
             addition to the cancer under study, for example, uncontrolled infections.

          2. Life-threatening illness, significant organ system dysfunction, or other condition
             that, in the investigator's opinion, could compromise subject safety, or the integrity
             of study outcomes, or interfere with the absorption or metabolism of ASTX295.

          3. History of, or at risk for, cardiac disease, as evidenced by any of the following
             conditions:

               1. Abnormal left ventricular ejection fraction.

               2. Congestive cardiac failure of ≥Grade 3.

               3. Unstable cardiac disease.

               4. History or evidence at Screening of long QT interval corrected for heart rate
                  (QTcF), ventricular arrhythmias, clinically significant bradyarrhythmias,
                  third-degree atrioventricular (AV) block, presence of cardiac pacemaker or
                  defibrillator, or other clinically significant arrhythmias.

               5. Screening 12-lead electrocardiogram (ECG) with measurable QTcF interval of ≥470
                  msec. (Fridericia's formula should be used).

          4. Known advanced human immunodeficiency virus (HIV) infection (including AIDS): clinical
             stage ≥ 3 according to WHO classification and/or HIV-associated immunodeficiency (CD4
             count less than 500 per mm3 of blood). Antiretroviral therapy (ART) is allowed
             (subjects should be on established ART for at least four weeks and have an HIV viral
             load less than 400 copies/mL prior to enrollment).

          5. Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (Inactive
             Hepatitis Carrier and subjects with laboratory evidence of no active replication on
             antivirals - viral load below limit of detection- will be permitted).

          6. Known brain metastases, unless previously treated and clinically stable for at least 4
             weeks with or without steroids.

          7. Known significant mental illness or other conditions, such as active alcohol or other
             substance abuse that, in the opinion of the investigator, predispose the subject to
             high risk of noncompliance with the protocol treatment or assessments.

             Prior/Concomitant Therapy

          8. Prior anticancer treatments or therapies within the indicated time window prior to
             first dose of study treatment (ASTX295), as follows:

               1. Cytotoxic chemotherapy within 3 weeks prior. Any encountered treatment-related
                  toxicities (excepting alopecia) must be stabilized or resolved to ≤Grade 1.

               2. Monoclonal antibodies, biologics, or immunotherapy within 4 weeks prior. Any
                  encountered treatment-related toxicities must be stabilized or resolved to ≤Grade
                  1.

               3. Molecularly targeted drug or other investigational drugs, without the potential
                  for delayed toxicity, within 4 weeks of the first dose of study treatment or 5
                  half-lives (minimum 14 days), whichever is shorter. Any encountered
                  treatment-related toxicities must be stabilized or resolved to ≤Grade 1.

               4. Major surgery or radiation within 4 weeks prior to first dose (palliative
                  radiotherapy to a single lesion within 2 weeks).

          9. Prior treatment with MDM2 antagonist

         10. Inability to swallow oral medication or inability or unwillingness to comply with the
             administration requirements related to ASTX295.

             Participants are excluded from the Phase 2 part of the study if any of the following
             additional criteria apply:

         11. Active malignancy other than the cancer under study (excludes low risk prostate
             cancer, basal cell carcinoma of the skin and superficial bladder cancer).