Inclusion Criteria

          1. Has a diagnosis of refractory or relapsed (R/R) AML or high-risk MDS:

               -  Part 1 and 1A (Dose Escalation)

                    -  Participants with R/R AML, OR

                    -  Participants with untreated, high-risk MDS or participants who have received
                       prior MDS treatment regimens.

                    -  Participants ≥18 years old.

               -  Part 2 (Dose Expansion)

                    -  Cohort 1: R/R AML

                         -  Participants who have treatment failure to prior AML therapy or have
                            relapsed after prior AML therapy.

                         -  Participants ≥18 years old.

                    -  Cohort 2: Newly diagnosed AML

                         -  Participants with newly diagnosed AML who are ineligible for intensive
                            induction chemotherapy. Participants must have had no prior AML
                            treatment, with the exceptions of therapy for antecedent hematologic
                            malignancies or hydroxyurea.

                         -  Participants ≥75 years old, OR Participants between 18 and 74 years old
                            (inclusive) with at least one of the specific protocol-defined
                            comorbidities.

                    -  Cohort 3: High-risk MDS

                         -  Participants with untreated, high-risk MDS or who received up to 2
                            prior MDS treatment regimens.

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

               -  As an exception, participants with newly diagnosed AML between 18 and 74 years
                  old (inclusive) in Part 2 Cohort 2 with ECOG Performance Status of 3 will be
                  eligible.

          3. Has protocol-defined adequate renal, hepatic and blood clotting functions.

          4. Is able to provide written informed consent (or authorized representative), comply
             with protocol visits and procedures, and take oral medication, and does not have any
             active infection or comorbidity that would interfere with therapy.

          5. If female, is either postmenopausal (no menstrual period for a minimum of 12 months),
             surgically sterile, or, if of childbearing potential, has a negative serum pregnancy
             test upon entry into this study and is willing to use maximally effective birth
             control during the period of therapy and for 6 months following the last
             investigational drug dose.

               -  If male, is surgically sterile or willing to use a maximally effective
                  double-barrier contraception method upon enrollment, during the course of the
                  study, and for 6 months following the last investigational drug dose.

          6. Is fully informed about their illness and the investigational nature of the study
             protocol (including foreseeable risks and possible side effects).

          7. Signs and dates an Institutional Review Board-approved informed consent form
             (including Health Insurance Portability and Accountability Act authorization, if
             applicable) before performance of any study-specific procedures or tests.

          8. Is able and willing to provide bone marrow biopsies/aspirates as requested by the
             protocol.

          9. Is willing to undergo malignancy genotyping for TP53 mutation, insertion, or deletion
             at screening.

        Exclusion Criteria

          1. Has a diagnosis of acute promyelocytic leukemia.

          2. Has a malignancy that is known to contain a non-synonymous mutation, insertion, or
             deletion in the TP53 gene determined previously or at screening.

          3. Has presence of central nervous system (CNS) involvement of leukemia or a history of
             primary CNS leukemia.

          4. Has a second concurrent primary malignancy that required active treatment within the
             previous 2 years, except for localized cancers that have apparently been cured, such
             as non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the
             cervix or breast.

          5. Has any condition that would preclude adequate absorption of DS-3032b, including
             refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel
             resection, and/or graft-versus-host disease (GVHD) affecting the gut.

          6. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals,
             known human immunodeficiency virus infection, or active hepatitis B or C infection.

          7. Has a concomitant medical condition that would increase the risk of toxicity.

          8. Has unresolved toxicities from previous anticancer therapy, defined as toxicities
             (other than alopecia) not yet resolved to NCI-CTCAE Grade ≤ 1, or baseline. Subjects
             with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator
             and Sponsor (eg, Grade 2 chemotherapy-induced neuropathy).

          9. Has received Hematopoietic Stem Cell Transplantation (HSCT) within 60 days of the
             first dose of study drugs or has clinically significant GVHD or GVHD requiring
             initiation of systemic treatment or systemic treatment escalation within 21 days prior
             to Screening and/or >Grade 1 persistent or clinically significant GVHD or other
             non-hematologic toxicity related to HCT.

         10. Is receiving concomitant treatment with a strong inhibitor or inducer of cytochrome
             P450 3A4/5.

         11. Has received any therapies intended to treat malignancy within 7 days (small
             molecules) or 21 days (anti-body/immune based biologics) of first receipt of study
             drugs [except for hydroxyurea, which must be discontinued at least 48 hours (Day -2)
             prior to study treatment].

         12. Had major surgery within 4 weeks prior to study drug treatment.

         13. Participated in a therapeutic clinical study within a washout time of 2 weeks or 5
             half-lives of the drug/biologic (whichever is longer) before starting study drug
             treatment under this protocol, or current participation in other therapeutic
             investigational procedures.

         14. Has prolongation of corrected QT interval using Fridericia's method (QTcF) at rest,
             where the mean QTcF interval is > 480 ms based on triplicate electrocardiograms
             (ECGs).

         15. Is pregnant or breastfeeding.

         16. Has substance abuse or medical, psychological, or social conditions that, in the
             opinion of the Investigator, may interfere with the subject's participation in the
             clinical study or evaluation of the clinical study results.

         17. Prior treatment with an MDM2 inhibitor.