A Phase 2 Study Evaluating Olutasidenib in Patients With IDH1-mutated Clonal Cytopenia of Undetermined Significance and Lower-risk Myelodysplastic/Syndromes/Chronic Myelomonocytic Leukemia.

Inclusion Criteria:

1. Pathologically proven CCUS or lower-risk MDS/CMML.

2. CCUS is defined as the presence of cytopenia (absolute neutrophil count < 1.8 x 10^9/L, hemoglobin < 13 g/dL in males or < 12 g/dL in females, and/or platelets < 150 x 10^9/L) for at least 30 days that are otherwise unexplained and with nodiagnostic hematopathologic features of myeloid neoplasms. Patients with knownDuffy-null phenotype must have absolute neutrophil counts less than their lowerlimit of normal.

3. Lower-risk MDS/CMML includes patients with International Prognostic ScoringSystem (IPSS) low- or intermediate-1-risk disease and Revised IPSS (IPSS-R)score ≤ 3.5 and Molecular IPSS (IPSS-M) very low-, low-, or moderate low-riskcategories.

4. Patients must have a documented IDH1 mutation with variant allele frequency (VAF) ≥ 0.02.

5. Patients ≥ 18 years old.

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

7. Bilirubin ≤ 2 times upper limit of normal (ULN) or ≤ 3 times ULN in patients withGilbert Syndrome.

8. Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase ≤ 3 times ULN.

9. Acceptable renal function with serum creatinine ≤ 1.5 times ULN or calculatedcreatinine clearance ≥ 50 mL/min (as assessed by Cockcroft-Gault, Modification ofDiet in Renal Disease Formula [MDRD], or Chronic Kidney Disease Epidemiology [CKD-Epi] validated measures).

10. Negative serum or urine pregnancy test if female of childbearing potential.

11. For fertile men and women, agreement to use highly effective contraceptive methodsfor the duration of study participation and 90 days after the last dose of studymedication. Appropriate highly effective method(s) of contraception include oral orinjectable hormonal birth control, intrauterine device (IUD), and double barriermethods (for example a condom in combination with a spermicide).

12. Agreement for male patients not to donate sperm and for female patients ofchildbearing potential not to donate ova during the study and for 90 days after thefinal dose of study drug.

13. Ability and willingness to signed informed consent prior to beginning study andundergoing procedures.

Exclusion Criteria:

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

2. Patients with any concurrent uncontrolled clinically significant medical condition,including life-threatening severe infection or psychiatric illness, which couldplace the patient at unacceptable risk of study treatment.

3. Known active hepatitis B (hepatitis B virus [HBV]) or hepatitis C (hepatitis C virus [HCV]) or HIV infection.

4. Pregnant or nursing women or women of childbearing potential not using highlyeffective contraception; male patients not using highly effective contraception asdefined in the inclusion criteria.

5. Subject with white blood cell count > 25 x10^9/L.

• Note: hydroxyurea use is permitted to meet this criterion with no washoutrequired.

6. Unwillingness or inability to comply with procedures either required in thisprotocol or considered standard of care.