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 109/L, hemoglobin < 13 g/dL in males or < 12 g/dL in females, and/or platelets < 150 x 109/L) for at least 30 days that are otherwise unexplained and with nodiagnostic hematopathologic features of myeloid neoplasms.

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. Participants must have a documented IDH1 mutation with VAF ≥ 0.02

5. Participants ≥ 18 years old

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

7. Acceptable liver function

8. Bilirubin ≤ 2 times upper limit of normal (ULN) or ≤ 3 times ULN inparticipants with Gilbert Syndrome

9. Aspartate transaminase (AST), alanine transaminase (ALT), and alkalinephosphatase ≤ 3 times ULN

10. Acceptable renal function with serum creatinine ≤ 1.5 times ULN or calculatedcreatinine clearance ≥ 50 mL/min (as assessed by Cockcroft-Gault, MDRD, or CKD-Epivalidated measures)

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

12. 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)

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

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

Exclusion Criteria:

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

2. Participants with any concurrent uncontrolled clinically significant medicalcondition, including life-threatening severe infection or psychiatric illness, whichcould place the patient at unacceptable risk of study treatment

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

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

5. Participant with white blood cell count > 25 x109/L Note: hydroxyurea use ispermitted to meet this criterion with no washout required

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