A Pivotal Study of HQP1351 in Patients With Chronic Myeloid Leukemia in Chronic Phase

Prior treatment

• Received cytotoxic chemotherapy or radiotherapy within 28 days prior to the first administration, interferon or cytarabine or antitumor effect Chinese herbal medicine or Chinese patent medicine within 14 days prior to the first administration, or targeted BCR-ABL1 TKI within 7 days prior to the first administration, or hydroxyurea or anagrelide within 24 hours after the first administration, or adverse events (except alopecia) caused by previous treatment and have not recovered.
• The patients who received any other investigating drugs within 14 days prior to first administration.
• For patients with CML-CP, if they have progressed to AP or BP, they cannot be enrolled after treatment with CML-CP.
• Patients who are currently receiving treatment with a medication that has the potential to interact with research drug.
• Have previously been treated with ponatinib or HQP1351 (or drugs of similar composition).
• Have a history of serious cardiovascular diseases during the previous treatment of chronic myeloid leukemia with TKI, including myocardial infarction, unstable angina pectoris, severe arrhythmia and congestive heart failure.
• Underwent autologous or allogeneic stem cell transplant.
• Have diseases with abnormal bleeding and coagulation function, or have a bleeding disorder unrelated to CML within 3 months before first dose of study drug.
• Underwent major surgery (except minor surgical procedures, such as placement or bone marrow biopsy) with 14 days prior to the first dose of study drug.
• Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy (It is defined as a daily dose of corticosteroids less than 30 mg prednisone or the same amount of other corticosteroids within 7 days).

Other illness

• Absorption disorder syndrome or other diseases affecting oral drug absorption.
• Pulmonary systolic pressure (PSP) of echocardiography is more than 50 mmHg, or there is clinical symptom related to pulmonary hypertension.
• Have active nervous system (CNS) disease as evidence by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required.
• History of another primary malignancies.
• Active symptomatic infection.
• Known to be allergic to study drug ingredients or their analogues.
• Suffer from any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the research drug.

Lab values

• Have any history of heart or vascular disease, such as hypertension (systolic blood pressure (HBP) \> 140mmHg and/or diastolic blood pressure \> 90mmHg), or take medications that are known to cause QT interval prolongation. The patients with well controlled HBP can be included.

Other

• CML-CP patient currently diagnosed as Complete cytogenetic response (CCyR).
• Female patients with blood β-Human chorionic gonadotropin positive, pregnant or lactating or expecting pregnancy during the study program.

• Male or non-pregnant, non-lactating female patients who are 18 years of age or older.
• CML-CP patients with positive Ph chromosome or BCR-ABL fusion genes.
• Resistance and intolerance of first- and second-generation TKIs: defined as resistance or intolerance to imatinib, nilotinib, and dasatinib.
• Ability to understand and willingness to sign a written informed consent form. The consent form must be signed by the patient prior to any study specific procedures.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Predicted life expectancy of ≥3 months.
• Organ function as indicated by the following laboratory indicators must be met (Hematological indicators require that no blood transfusion or any blood products or cytokines be used within 14 days prior to testing):
  • Hemoglobin ≥8.0g/dL.
  • White blood cell count ≥ 3.0×10\^9/L.
  • Platelet count ≥ 75×10\^9/L.
  • Serum creatinine ≤ 1.5×upper limit of normal (ULN) or 24 hours calculated creatinine clearance ≥ 50mL/min when serum creatinine \>1.5×ULN.
  • Serum albumin ≥ 3.0 g/dL.
  • Total bilirubin ≤ 1.5 x ULN.
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN.
  • Amylase≤1.5×ULN. Lipase≤1.5×ULN.
  • PT/APTT/INR≤1.5×ULN.
• Cardiac function index: ejection fraction (EF) \> 50%, pulmonary arterial systolic pressure (PASP) ≤50 mmHg.
• QT interval corrected on electrocardiogram (ECG) evaluation: QTc≤450ms in males or ≤470ms in females.
• Males and females of childbearing potential and their partners voluntarily take contraceptive measures that the researchers believe are effective within 120 days from the signing of the informed consent to the last use of the research drug, or confirm that sterilization has been performed (at least one month before screening).
• Willingness and ability to comply with study procedures and follow-up examination.