Overview

Evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ICP-248 in combination with azacitidine in patients with acute myelogenous leukemia and Myelodysplastic Syndromes.

Eligibility

Inclusion Criteria:

• Eligible subjects must meet all of the following criteria:
  1. Subject must have confirmation of diagnosis of AML (except for acute promyelocytic leukemia [APL]) or MDS per 2016 World Health Organization (WHO) criteria.
  2. For AML (except for APL) cohort:
     1. Previously treated relapsed/refractory AML subjects
     2. Treatment-naïve AML subjects should be:
        • 60 years of age OR ≥18 years and <60 years will be eligible if the subject has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy
  3. For MDS cohort:

     Adult TN MDS and R/R MDS: revised International Prognostic Scoring System (IPSS-R) score > 3 and bone marrow blasts ≥ 5%.

  4. Subject must have a projected life expectancy of at least 12 weeks.
  5. Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft-Gault formula.
  6. Subject must have adequate liver function

Exclusion Criteria:

1. R/R AML or R/R MDS with no response or intolerance to post azacitidine or BCL-2i.
2. Subject has acute promyelocytic leukemia (French-American-British Class M3 AML) or AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1.
3. Subject has known central nervous system (CNS) leukemia.
4. Suggest patients with active hepatitis B or C virus infection
5. History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
6. Subjects have another active malignancy within the past 2 years before study entry, except for curatively treated.