TGRX-678 Chinese Phase I in Chronic Myelogenous Leukemia (CML) Patients

Inclusion Criteria:

• Willing to participate in the study with informed consent;

• 18-75 years of age at the time of screening;

• Male or female;

• Diagnosis of CML-CP by cytomorphological examination of the bone marrow, molecularbiology examination, or cytogenetic testing during the screening period (accordingto the NCCN guidelines (NCCN, 2021);

• Received prior treatment with imatinib, dasatinib or nilotinib; patients must beintolerant or resistant to the above drugs according to MD Anderson or ELNguidelines;

• ECOG performance status ≤ 2;

• Minimum life expectancy of 3 months;

• Adequate renal function, defined as serum creatinine <1.5× upper limit of normality (ULN)

• Adequate liver function, defined as total bilirubin <1.5× ULN, AST and ALT <2.5×ULN;if liver function is compromised due to CML, AST and ALT <5×ULN;

• Adequate coagulation function, defined as PT<1.5×ULN, INR<1.5×ULN, and APTT<1.5×ULN;

• Normal pancreatic function, defined as lipase and amylase <1.5× ULN;

• Normal QTc interval, defined as ≤450 ms in males and ≤470 ms in females, asindicated by ECG screening results;

• For women with child-bearing potential, negative pregnancy test result at screeningperiod;

• Pregnant or breast feeding and female patients of childbearing potential must agreeto use effective methods of contraception.

Exclusion Criteria:

• Received TKI treatment within 7 days of first dosing of the investigational drug, orAEs related to previous treatment has not been recovered to Grade 1 or lower (exceptfor alopecia);

• Exposure to other antineoplastic therapies and either of the following: hydroxyureaor anagrelide within 24 h prior to the first dose; interferon or immunotherapywithin 14 days prior to the first dose, or any other cytotoxic chemotherapy,radiotherapy, or investigational therapy (excluding any TKI therapy) within 28 daysprior to the first dose;

• Stem cell transplant < 60 days prior to the first dose, with evidence of graftversus host disease (GVHD) or GVHD requiring immunosuppressive therapy;

• Concomitant immunosuppressive therapy (other than short term corticosteroidtreatment);

• Exposure to drugs related to torsade de pointes within 1 month of the screeningperiod;

• Cytological or pathological diagnosis of active central nervous system disorder;

• CML-CP patients already achieved complete cytogenetic response;

• CML-AP patients already achieved major hematological response;

• Significant uncontrolled cardiac disease;

• Uncontrolled hypertension (Diastolic BP > 85mm Hg; Systolic > 145 mm Hg; achievedwith or without medication);

• Exposure to herbal preparations or over-the-counter medications containing herbalingredients within 2 weeks prior to the first dose;

• Severe hemorrhagic disorders unrelated to CML;

• History of grade 3-4 pancreatitis or history of alcohol abuse;

• Uncontrolled hyper-triglyceridemia (TG>450 mg/dL);

• Malabsorption syndrome or other illness that could affect oral absorption;

• Diagnosis of another primary malignancy in the past 3 years (other than non-melanomaskin cancer, cervical carcinoma in situ, or controlled prostate cancer that havebeen cured within 3 years;

• Invasive/extensive surgery within 14 days prior to initiating TGRX-678 therapy;

• Active clinically significant infections, including syphilis, HIV, Hepatitis B orHepatitis C;

• Other criteria in the opinion of the investigator or the medical monitor that isunsuitable for the study, including diseases that could compromise the patientssafety or the evaluation of the drugs safety or poor compliance.