HPB-092 for the Treatment of Relapsed and Refractory Acute Myeloid Leukemia (NCT07137637) | Clinical Trial Compass
Not Yet RecruitingPhase 1
HPB-092 for the Treatment of Relapsed and Refractory Acute Myeloid Leukemia
60 participantsStarted 2025-12
Plain-language summary
HPB-092 effectively inhibits Fms-like tyrosine kinase 3 (FLT3) mutants with comparable or superior potency to approved FLT3 inhibitors and demonstrates improved selectivity, potentially reducing toxicity. Its highly selective and potent inhibition of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) may provide additional therapeutic benefits that could enhance treatment efficacy and durability for patients with relapsed or refractory acute myeloid leukemia (RR-AML), further improving clinical outcomes in this population. HPB-092 also has a favorable safety profile, with no major risks identified in preclinical studies.
Phas 1 Study Outline:
1. This is a multicenter, open-label, phase 1 study to evaluate the safety and efficacy of oral HPB-092 as monotherapy in patients with RR-AML.
2. The study aims to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy.
3. It consists of two parts: Part A for dose escalation and Part B for dose expansion, involving single or multiple doses.
4. Patients must be diagnosed with morphologically documented RR-AML according to World Health Organization (WHO) 2022 criteria.
5. Baseline assessments will include RR-AML with FLT3 mutations, spliceosome mutations in SF3B1 and U2AF1, as well as other biomarkers, which will be monitored throughout the study.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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:
✓. The patients should have a stable transfusion requirement prior to enrollment as specified in the protocol.
✓. Male or non-pregnant, non-lactating female patients aged 18 years or older.
✓. The patient is not suitable for other known therapies that have clinical benefits for the disease.
✓. Life expectancy of ≥12 weeks, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
✓. 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.
✓. 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.
What they're measuring
1
Adverse Events and Treatment-Emergent Adverse Events [Safety and Tolerability]
Timeframe: From the first dose (Cycle 1 day 1) of HPB-092 treatment until 28 days after the completion of treatment, or after early termination or withdrawal from the study, with a duration of up to 24 months
2
Dose-Limiting Toxicity [Safety and Tolerability]
Timeframe: Days 1-28 of the first cycle (each cycle is 28 days)
3
Maximum Tolerated Dose [Safety and Tolerability]
Timeframe: Days 1-28 of the first cycle (each cycle is 28 days)
✓. For females of childbearing potential, a serum pregnancy test must be negative within 7 days before enrollment.
Exclusion criteria
✕. Diagnosed with acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia.
✕. The patient has had a malignancy other than AML within the past five years as specified in the protocol.
✕. The patient has persistent non-hematological toxicities of ≥ Grade 2 (per CTCAE v5.0) from prior treatment.
✕. History of Hematopoietic Stem Cell Transplant (HSCT) as specified in the protocol.
✕. The patient has clinically active central nervous system (CNS) leukemia.
✕. The patient has a disseminated intravascular coagulation (DIC) abnormality.
✕. Recent surgery or radiation therapy as specified in the protocol.
✕. 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.