HPB-092 for the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible for enrollment in the study:

1. The patient must have a diagnosis of morphologically documented relapsed or refractory acute myeloid leukemia (AML) according to the World Health Organization (WHO) 2022 criteria, and must meet one of the following conditions:

   Relapsed Disease: Bone marrow blasts ≥ 5%; or Reappearance of blasts in the peripheral blood in at least two separate samples taken at least one week apart; or Development of extramedullary disease. Refractory Disease: Failure to achieve CR, CRh, or CRi at the response landmark (e.g., after 2 courses of intensive induction therapy), or Failure to achieve remission by a defined landmark, e.g., 180 days after initiation of less intensive therapy.
2. The patients should have a stable transfusion requirement prior to enrollment as specified in the protocol.
3. Male or non-pregnant, non-lactating female patients aged 18 years or older.
4. The patient is not suitable for other known therapies that have clinical benefits for the disease.
5. Life expectancy of ≥12 weeks, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
6. Renal Function: Serum creatinine \<1.5× the upper limit of normal (ULN) or Estimated creatinine clearance ≥ 60 mL/min as calculated using a standard method \[Cockcroft-Gault formula, Modification of Diet in Renal Disease (MDRD) equation, or estimated glomerular filtration rate (eGFR) calculation\]. Liver Function: Total serum bilirubin ≤1.5× ULN unless the patient has liver involvement by the primary disease (≤3× ULN); and AST and ALT ≤2.5× ULN unless the patient has hepatic metastasis (≤5× ULN). Cardiac Function: Left ventricular ejection fraction (LVEF) \>50% as measured by echocardiogram or MUGA scan.
7. Acute effects of any prior therapy must be resolved to baseline severity or Grade ≤ 1 per CTCAE v5.0, except for adverse events (AEs) that do not constitute a safety risk according to the investigator's judgment.
8. For females of childbearing potential, a serum pregnancy test must be negative within 7 days before enrollment.
9. Male and female patients of childbearing potential who are at risk for pregnancy must agree to use at least two highly effective methods of contraception throughout the study and for at least 90 days (or 180 days if required by local regulations) after the last dose of the assigned treatment.
10. The interval from prior treatment to the time of study drug administration must be at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents.
11. The patient must have the ability to understand and be willing to sign the informed.

Exclusion Criteria:

Patients with any of the following characteristics/conditions will not be able to enroll in the study:

1. Diagnosed with acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia.
2. The patient has had a malignancy other than AML within the past five years as specified in the protocol.
3. The patient has persistent non-hematological toxicities of ≥ Grade 2 (per CTCAE v5.0) from prior treatment.
4. History of Hematopoietic Stem Cell Transplant (HSCT) as specified in the protocol.
5. The patient has clinically active central nervous system (CNS) leukemia.
6. The patient has a disseminated intravascular coagulation (DIC) abnormality.
7. Recent surgery or radiation therapy as specified in the protocol.
8. History of Class 3 or more severe heart failure according to NYHA classification, or left ventricular ejection fraction (LVEF) below 45%, or Fridericia-corrected QT interval (QTcF) \> 450 ms at screening.
9. The patient has hypokalemia or hypomagnesemia at screening.
10. The patient requires treatment with drugs that are strong inhibitors or inducers of CYP3A4 or P-glycoprotein (P-gp) as specified in the protocol.
11. Active graft-versus-host disease (GVHD) and immunosuppressive treatment as specified in the protocol.
12. Use of systemic corticosteroids or immunosuppressive drugs as specified in the protocol.
13. The patient is known to be infected with human immunodeficiency virus (HIV), active hepatitis B or C, or other active hepatic disorders. The patient has an active uncontrolled infection.
14. The patient has any condition that, in the investigator's opinion, makes the patient unsuitable for study participation.