• For HQP1351 monotherapy, patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL, with or without T315I mutation

• For Cohort D, patients with Ph+ BCP ALL or CML LBP must be resistant or intolerant to at least one second or later generation TKI, such as dasatinib, nilotinib, bosutinib and ponatinib, despite optimal supportive care

• For HQP1351 monotherapy only: Be previously treated with and developed resistance or intolerance to at least two TKIs including ponatinib, imatinib, dasatinib, nilotinib, bosutinib, and asciminib. For patients with a T315I mutation, number of pretreated TKIs is not restricted.

‣ The definition of resistance to first-line TKI treatment refers to European Leukemia Net (ELN) recommendations. The definitions are the same for patients in CP, AP, BP, and Ph+ ALL, and apply also to second-line treatment, when first-line treatment was changed for intolerance. The patients must meet at least one criterion:

• Three months after the initiation of therapy: non-complete hematologic response (CHR) and/or Ph+ \>95%

∙ Six months after the initiation of therapy: BCR-ABL1\>10% and/or Ph+ \>35%

∙ Twelve months after the initiation of therapy: BCR-ABL1\>1% and/or Ph+ \>0%

∙ Then, and at any time after the initiation of therapy: Loss of CHR, or loss of complete cytogenetic response (CCyR), or confirmed loss of major molecular response (MMR) (In 2 consecutive tests, of which one with a BCR-ABL1 transcripts level ≥1%), mutations, clonal chromosome abnormalities in Ph+ cells (CCA/Ph+)

⁃ The definition of resistance to second-line TKI treatment

‣ a) For CML CP patients: the patients must meet at least one criterion as follows:

‣ i.) Three months after the initiation of therapy: No CHR or Ph+ \>95% or new mutations

‣ ii.) Six months after the initiation of therapy: BCR-ABL1\>10% and/or Ph+ \>65% and/or new mutations

‣ iii.) Twelve months after the initiation of therapy: BCR-ABL1\>1% and/or Ph+ \>35% and/or new mutations

‣ iv.) Then, and at any time after the initiation of therapy: Loss of CHR or loss of CCyR, new mutations, confirmed loss of MMR (In 2 consecutive tests, of which one with a BCR-ABL1 transcripts level ≥1%), clonal chromosome abnormalities in Ph+ cells (CCA/Ph+)

‣ b) For CML AP patients: the patients must meet at least one criterion as follows:

‣ i.) Three months after the initiation of therapy: failure to achieve a major hematologic response (MaHR)

‣ ii.) At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 4 weeks

‣ iii.) At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of a MaHR

‣ c) For CML BP and Ph+ ALL patients: the patients must meet at least one criterion as follows:

‣ i) One month after the initiation of therapy: failure to achieve a MaHR

‣ ii) At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 1 week

‣ iii) At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of a MaHR

⁃ Intolerance to TKIs is defined as:

• Non-hematological AEs: patients with grade 3 or 4 toxicity during TKIs treatment, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments in the absence of a CCyR for CP patients or MaHR for AP/BP or Ph+ ALL patients

∙ Hematological AEs: patients with grade 3 or 4 toxicity during TKIs treatment, that is recurrent after unresponsive after optimal management, including dose adjustments in the absence of a CCyR for CP patients or MaHR for AP/BP or Ph+ ALL patients

• Patients providing written informed consent before initiation of any study-related activities

• Eastern Cooperative Oncology Group (ECOG) performance status ≤2

• Minimum life expectancy of 3 months or more

• Patients with adequate organ function as defined below:

‣ Creatinine \< 2 × upper limit of normal (ULN); or, creatinine \> 2 × ULN, with 24h glomerular filtration rate (GFR) ≥ 30 mL/min (Cockcroft-Gault)

⁃ Serum albumin ≥ 3.0 g/dL

⁃ Total bilirubin \< 1.5 × ULN

⁃ Aspartate aminotransferase (AST \[Serum glutamic oxaloacetic transaminase (SGOT)\]) and alanine aminotransferase (ALT \[serum glutamate-pyruvate transaminase (SGPT)\]) \< 3 × ULN for institution (\<5×ULN if liver involvement with leukemia)

⁃ Serum amylase and lipase ≤ 1.5 × ULN

⁃ Prothrombin time (PT) ≤ 1.5 × ULN

• Heart function: Left ventricular ejection fraction (LVEF) \> 50%

• Normal QT interval corrected Fridericia (QTcF) interval on screening electrocardiogram (ECG) evaluation: male ≤450ms, female ≤470ms

• For females of childbearing potential, a negative pregnancy test must be established before enrollment. And the eligible female and male patients with childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study

• Ability to comply with study procedures, in the Investigator's opinion