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 of child-bearing potential or male subject with female partner of child-bearing potential.

Exclusion Criteria

• Exposure to other antineoplastic therapies prior to study enrollment;
• Exposure to other investigational agent(s) within 14 days of initiating TGRX-678 therapy;
• Ongoing toxicity from prior therapy greater than grade 1 by CTCAE v. 3 (except alopecia);
• Hematopoietic cell transplantation < 60 days prior to the first dose;
• Evidence of graft versus host disease (GVHD), whether or not requiring immunosuppressive therapy;
• Concomitant immunosuppressive therapy (other than short-term corticosteroid treatment);
• 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 clinical protocol;
• Having long QT syndrome, or with family history of idiopathic sudden death or congenital long QT syndrome;
• Uncontrolled hypertension;
• Receipt of Traditional Chinese medication or herbal preparations indicated for anti-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 4 weeks 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 result for 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 partners of child-bearing potential that is unable or unwilling to take highly effective contraceptive measures during the trial and for 6 months after last dose of investigational drug;
• Significant organ dysfunction that could compromise the patient's safety or the evaluation of the drug's safety in the opinion of the investigator or the medical monitor;
• Any condition makes participation in this trial inappropriate in the opinion of the investigator or medical monitor;