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

Prior treatment

• Received TKI treatment within 7 days of first dosing of the investigational drug, or AEs related to previous treatment has not been recovered to Grade 1 or lower (except for alopecia);
• Exposure to other antineoplastic therapies and either of the following: hydroxyurea or anagrelide within 24 h prior to the first dose; interferon or immunotherapy within 14 days prior to the first dose, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy (excluding any TKI therapy) within 28 days prior to the first dose;
• Stem cell transplant \< 60 days prior to the first dose, with evidence of graft versus host disease (GVHD) or GVHD requiring immunosuppressive therapy;
• Concomitant immunosuppressive therapy (other than short term corticosteroid treatment);
• Exposure to drugs related to torsade de pointes within 1 month of the screening period;
• Exposure to herbal preparations or over-the-counter medications containing herbal ingredients within 2 weeks prior to the first dose;
• Invasive/extensive surgery within 14 days prior to initiating TGRX-678 therapy;

Other illness

• Cytological or pathological diagnosis of active central nervous system disorder;
• Significant uncontrolled cardiac disease;
• Uncontrolled hypertension (Diastolic BP \> 85mm Hg; Systolic \> 145 mm Hg; achieved with or without medication);
• Severe hemorrhagic disorders unrelated to CML;
• History of grade 3-4 pancreatitis or history of alcohol abuse;
• Malabsorption syndrome or other illness that could affect oral absorption;
• Diagnosis of another primary malignancy in the past 3 years (other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled prostate cancer that have been cured within 3 years;
• Active clinically significant infections, including syphilis, HIV, Hepatitis B or Hepatitis C;
• Other criteria in the opinion of the investigator or the medical monitor that is unsuitable for the study, including diseases that could compromise the patients safety or the evaluation of the drugs safety or poor compliance.

Lab values

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

Other

• CML-CP patients already achieved complete cytogenetic response;
• CML-AP patients already achieved major hematological response;

• 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, molecular biology examination, or cytogenetic testing during the screening period (according to the NCCN guidelines (NCCN, 2021);
• Received prior treatment with imatinib, dasatinib or nilotinib; patients must be intolerant or resistant to the above drugs according to MD Anderson or ELN guidelines;
• 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, as indicated by ECG screening results;
• For women with child-bearing potential, negative pregnancy test result at screening period;
• Pregnant or breast feeding and female patients of childbearing potential must agree to use effective methods of contraception.