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

A Single-arm, Open-label, Multi-center Phase II Study Evaluating Efficacy and Safety of TGRX-678 in CML-AP Patients Relapsed or Refractory From 3rd-generation TKI Treatment

A Phase II study evaluating the safety and efficacy of TGRX-678 in Chronic Myelogenous Leukemia (CML) patients in Accelerated phase (AP) and are relapsed or refractory from third-generation Tyrosine Kinase Inhibitor (TKI) treatment

This Phase II study is of single-arm, open-label and multi-center designs to study safety and efficacy profiles of TGRX-678 in CML-AP patients. Patients need to have medical history of failing treatment(s) from third-generation TKI drugs. Patients with or without T315I mutation is enrolled.

Inclusion Criteria:

• Willing to consent
• 18 years of age or above at time of screening; both sexes eligible
• Relapsed or refactory from 3rd-generation Tyrosine kinase inhibitor (TKI) treatment
• For patients without T315I mutation, the patients must received 1st, 2nd and 3rd generation TKI
• For patients with T315I mutation, the patients much received Olverembatinib or Ponatinib treatment
• Diagnosis of CML-AP by bone marrow morphological test, molecular biology test or cytogenetic tests
• ECOG score </=2
• Minimum life expectancy of at least 3 months
• Adequate hematological indicators
• Adequate kidney function
• Adequate liver function
• Adequate coagulation function
• Adequate pancreatic function
• Adequate QTc interval as confirmed by electrocardiogram (ECG) test
• Negative pregnancy result at screening for female patients of child-bearing potential
• Willing to take contraceptive measure during the study (For male and female patients of child-bearing potential)

Exclusion Criteria:

• Reception of TKI treatment or presence of unrecovered TKI treatment related non-hematological adverse events within 7 days of first dose
• Reception of other anti-tumor treatments
• In need for immune suppressive treatment
• Usage of drugs associated with Torsades de Pointes within 1 months before screening
• Presence of other medical conditions that require using treatment that may have drug-drug interaction with the investigational drug
• History of hemapoietic stem cell transplant
• Presence of active central nervous system conditions
• CML-AP patients who already reached major hematological response
• CML-AP patients who used to progress to Blast Phase (BP)
• Presence or having uncontrolled condition for cardiovascular diseases
• History of any heart or cardiovascular conditions (except for patients with hypertension which is controlled by anti-hypertensive drugs, and blood pressure is controlled at no higher than 160/100 mmHg for 1 months before screening)
• Usage of any Traditional Chinese Medicine indicated for anti-tumor purpose 2 weeks before first dose
• Severe hemorrhagic disease unrelated to CML
• History of severe cardiovascular condition during past TKI treatment for CML
• History of pancreatic inflammation or alcohol abuse within 3 years before first dose
• Uncontrolled Hypertriglyceridemia
• Presence of malabsorption or other conditions that may affect drug absorption
• Diagnosis of other primary malignant tumor within 5 years
• Reception of major surgery 14 days before first dose
• Presence of continuous or active infection (including HIV, hepatitis B, hepatitis C)
• Presence of other conditions that the investigators or medical monitor deem unfit for the study