TQ05105 Tablet for Myelofibrosis Treatment in Ruxolitinib-Resistant or Intolerant Patients

A Phase Ib Study of TQ05105 Tablets for the Treatment of Intermediate and High Risk Myelofibrosis Refractory/Relapsed/Intolerant to Ruxolitinib

This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy of TQ05105 Tablets in patients with intermediate-risk and high-risk myelofibrosis.

Inclusion Criteria:

• Subjects voluntarily participated in this study, signed informed consent forms, and demonstrated good compliance；
• Age: 18 or older (when signing the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 2; Life expectancy ≥ 24 weeks;
• Patients diagnosed with Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), or post essential thrombocythemia myelofibrosis (post-ET MF);
• According to the dynamic international prognostic scoring system (DIPSS), patients with intermediate or high risk of bone marrow fibrosis were evaluated;
• Patients with poor efficacy or intolerant of Ruxolitinib;
• Spleen enlargement;
• Peripheral blood primary cells and bone marrow primary cells were ≤10%;
• No growth factor, colony stimulating factor, thrombopoietin or platelet transfusion was received within 2 weeks before the examination, and the blood routine indexes met the requirements within 7 days before the first administration;
• The Main organ function is normal;
• Men and women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study. Serum human chorionic gonadotrophin（HCG）test is not negative within 7 days before the first administration and must be non-lactating patients.

Exclusion Criteria:

• Patients who have previously received allogeneic stem cell transplantation, or received autologous stem cell transplantation within 3 months before the first administration, or recently planned stem cell transplantation;
• Previous treatment with JAK inhibitors(except ruxolitinib);
• Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
• Other malignancies within 3 years prior to first administration or currently present;
• Patients with multiple factors (such as inability to swallow, postoperative gastrointestinal resection, acute and chronic diarrhea, intestinal obstruction, etc.) affecting oral or absorption of drugs;
• The non-hematological toxicity caused by previous treatment did not return to grade≤1;
• Major surgical treatment or significant traumatic injury within 4 weeks prior to first administration;
• Presence of congenital bleeding disorder and congenital coagulopathy;
• Patients who had arterial/venous thrombosis events within 6 months before the first administration;
• Have a history of mental drug abuse, or have a mental disorder;
• Active or uncontrolled severe infection;
• Active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection and HCV RNA positive;
• Patients with ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia, QT interval prolongation and ≥ grade 2 congestive heart failure;
• Unsatisfactory blood pressure control despite standard therapy;
• Patients with renal failure requiring hemodialysis or peritoneal dialysis;
• Patients newly diagnosed with pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before the first administration;
• Patients with a history of immunodeficiency disease or organ transplantation;
• Patients with epilepsy requiring treatment;
• Use of any MF medications, any immunomodulators, androgens, any immunosuppressive agents, erythropoietin, aspirin > 100 mg/day within 2 weeks prior to first administration;
• Patients who have received Chinese patent medicines with anti-tumor indications specified in the approved drug package insert of China National Medical Products Administration (NMPA) within 2 weeks before the first administration;
• Patients with uncontrolled pleural effusion, pericardial effusion or ascites;
• There was a history of attenuated live vaccine inoculation within 4 weeks before the first administration, or attenuated live vaccine inoculation was planned during the study period;
• People with known hypersensitivity to the study drug and excipients;
• Patients diagnosed as active autoimmune diseases within 2 years before the first administration;
• Those who participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first administration;
• According to the judgment of the investigators, some situations seriously endanger the safety of the subjects or affect the subjects to complete the study.