ASTX727 and FT-2102 in Treating IDH1-Mutated Recurrent/Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

Inclusion Criteria:

• Must voluntarily sign an informed consent document (ICF)

• Morphologically confirmed diagnosis of MDS (inclusive of MDS/MPN) or AML in accordancewith World Health Organization (WHO) diagnostic criteria

• Phase Ib: Subjects may have

• Relapsed/refractory AML or MDS or

• Treatment naive AML

• Phase II Expansion: Subjects may have

• Relapsed/refractory AML or MDS or

• Treatment naive AML or

• Treatment naive MDS

• For patients with MDS, must have a Revised International Prognostics Scoring System (IPSS-R) risk category of intermediate, high, or very high

• Confirmed IDH1 R132 mutation

• A bone marrow biopsy must be performed and tissue collected for entrance to the trial

• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Life expectancy of at least 3 months in the assessment of the investigator

• Recovery from the non-hematologic toxic effects of prior treatment to grade =< 1, orbaseline value according to National Cancer Institute (NCI) Common TerminologyCriteria for Adverse Events (CTCAE) version (v)4.03 classification (excludinginfertility, alopecia, or grade 1 neuropathy)

• Must have adequate hepatic and renal function as demonstrated by the following: ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN); Direct bilirubin ≤ 1.5 xULN(or ≤ 2x ULN if due to Gilbert's disease); Serum creatinine of 1.5 x ULN or creatinineclearance of > 50 mL/min (whichever is lower)

• Baseline Fridericia's correction formula (QTcF) =< 450 msec (average of the QTcFvalues of screening triplicate electrocardiography [ECG]swith approximately two-minuteintervals ) except for those patients with a bundle branch block (BBB)

• For fertile men and women, agreement to use effective contraceptive methods for theduration of study participation and 90 days after the last dose of study medication

Exclusion Criteria:

• Treatment naive patients who are suitable for and willing to receive intensiveinduction chemotherapy

• Patients with active, uncontrolled infection. Patients with infection under activetreatment and controlled with antibiotics are eligible

• Concurrent condition that in the investigator's opinion would jeopardize compliancewith the protocol

• Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B,or C infection (hepatitis B carriers with normal liver function test [LFT]s andundetectable viral loads are allowed)

• Women who are pregnant or nursing

• Organ transplant recipients other than bone marrow transplant

• Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneichematologic stem cell transplant within 6 months. Grade II, or greater, activegraft-versus- host disease

• Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter)prior to the first dose of FT-2102/ASTX727. For investigational drugs for which 5half-lives is less than 21 days, a minimum of 10 days between termination of theinvestigational drug and administration of FT-2102/ASTX727 is required

• Any major surgery, chemotherapy, or immunotherapy within the last 21 days (limitedpalliative radiation is allowed >= 2 weeks); concurrent hydroxyurea is allowed if lessthan or equal to 2 grams daily

• Ongoing immunosuppressive therapy including systemic corticosteroids (prednisone orequivalent =< 20 mg daily allowed as clinically warranted). Patients are allowed touse topical or inhaled corticosteroids

• Concurrent condition that in the investigator's opinion would jeopardize compliancewith the protocol.

• Patients unable to swallow oral medications, or patients with gastrointestinalconditions (e.g., malabsorption, resection, etc.) deemed by the Investigator tojeopardize intestinal absorption

• Patients receiving intrathecal chemotherapy for active central nervous system (CNS)disease

• Patients who have exhibited allergic reactions to a previously administered IDH1inhibitor

• Patients with acute promyelocytic leukemia (APL)