TGRX-678 US Phase I for Subjects with Refractory or Advanced Chronic Myelogenous Leukemia

Inclusion Criteria:

• Willing to participate in the study with informed consent;

• At least 18 years of age at the time of screening;

• Any sex;

• Diagnosis of CML-CPduring the screening period;

• Intolerant or resistant to TKI treatments;

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

• Adequate Absolute neutrophil count (ANC), hemoglobin and platelets levels;

• Adequate renal and liver function;

• Normal corrected QT (QTcF) interval as indicated by electrocardiogram (ECG)screening results;

• Negative blood pregnancy test results for female patients of childbearing potential.

• Willing to take highly effective contraceptive measures throughout the trial and for 6 months after last dose of investigational drug for female subjects ofchild-bearing potential or male subject with female partner of child-bearingpotential.

Exclusion Criteria:

• Exposure to other antineoplastic therapies prior to study enrollment;

• Exposure to other investigational agent(s) within 14 days of initiating TGRX-678therapy;

• Ongoing toxicity from prior therapy greater than grade 1 by CTCAE v. 3 (exceptalopecia);

• Hematopoietic cell transplantation < 60 days prior to the first dose;

• Evidence of graft versus host disease (GVHD), whether or not requiringimmunosuppressive therapy;

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

• Exposure to drugs related to torsade de pointes;

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

• Significant or uncontrolled cardiovascular diseases as defined in the full clinicalprotocol;

• Having long QT syndrome, or with family history of idiopathic sudden death orcongenital long QT syndrome;

• Uncontrolled hypertension;

• Receipt of Traditional Chinese medication or herbal preparations indicated foranti-cancer purposes within 2 weeks prior to the first dose;

• Severe hemorrhagic disorders unrelated to CML;

• History of pancreatitis;

• History of excessive alcohol use;

• History of elevation in amylase or lipase within 1 year;

• Have Grade 2 or worse interstitial lung disease or interstitial pneumonitis within 4weeks prior to Screening;

• Uncontrolled hypertriglyceridemia;

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

• Diagnosis of another primary malignancy in the past 3 years;

• Reception of major surgery within 14 days prior to the first dose;

• Active infections that require systemic treatment or other severe infections within 14 days prior to enrollment;

• Known human immunodeficiency virus (HIV) positive; acute or chronic liver disease (including chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections);

• Have received or will receive a COVID-19 vaccine within 14 days of study enrollment;

• Have a positive reverse transcriptase polymerase chain reaction (RT-PCR) test resultfor SARS-CoV-2 within 2 weeks prior to Screening;

• Pregnant or breastfeeding female;

• Female patient of child-bearing potential or male patient who have female partnersof child-bearing potential that is unable or unwilling to take highly effectivecontraceptive measures during the trial and for 6 months after last dose ofinvestigational drug;

• Significant organ dysfunction that could compromise the patient's safety or theevaluation of the drug's safety in the opinion of the investigator or the medicalmonitor;

• Any condition makes participation in this trial inappropriate in the opinion of theinvestigator or medical monitor;