A Clinical Trial of TQ05105 Tablets Combined With TQB3909 Tablets in the Treatment of Myelofibrosis (MF)

Inclusion Criteria:

• Voluntarily participate in the study and signed informed consent with goodcompliance;

• Age: 18 or above (when signing the informed consent form); Eastern CooperativeOncology Group (ECOG) performance status (PS) score of 0 to 2; Life expectancy ≥ 24weeks;

• Patients diagnosed with Primary myelofibrosis (PMF), post polycythemia veramyelofibrosis (post-PV-MF), or post essential thrombocythemia myelofibrosis (post-ET-MF);

• Those with moderate or high risk myelofibrosis evaluated according to DynamicInternational Prognostic Scoring System (DIPSS) prognostic grading criteria, orthose with high risk myelofibrosis according to National Comprehensive CancerNetwork (NCCN) guidelines prognostic grading criteria;

• Patients with poor efficacy of JAK inhibitors (for monotherapy of TQB3909, phase Iband phase II cohort 2);

• Patients who had not received JAK inhibitor treatment (for phase Ib and phase IIcohort 2)

• Spleen enlargement;

• Peripheral blood primary cells and bone marrow primary cells are ≤10%;

• No growth factor, colony stimulating factor, thrombopoietin or platelet transfusionwas received within 2 weeks before the examination, and the blood routine indexesmet 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 duringthe study period and within 6 months after the end of the study.

Exclusion Criteria:

• Patients who have previously received allogeneic stem cell transplantation, orreceived autologous stem cell transplantation within 3 months before the firstadministration, or recently planned stem cell transplantation;

• Patients who have previously received BCL-2 inhibitor combined with JAK inhibitortherapy;

• Patients who have previously undergone splenectomy, or received splenic radiotherapywithin 6 months before the first administration;

• Other malignancies within 3 years prior to first administration or currentlypresent.

• Patients with multiple factors affecting oral or absorption of drugs;

• Major surgical treatment or significant traumatic injury within 4 weeks prior tofirst administration;

• Presence of congenital bleeding disorder and congenital coagulopathy;

• Patients who had arterial/venous thrombosis events within 6 months before the firstadministration.

• 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 , oractive Corona Virus Disease 2019 (COVID-19) infection;

• Patients with grade III or above congestive heart failure, unstable angina pectorisor myocardial infarction, or arrhythmia requiring treatment, or QT intervalprolongation within 6 months before the first administration;

• 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-relatedinterstitial lung disease within 3 months before the first administration;

• Patients with a history of immunodeficiency disease or organ transplantation;

• Patients with epilepsy requiring treatment;

• Patients with uncontrolled pleural effusion, pericardial effusion or ascites;

• There is a history of attenuated live vaccine inoculation within 4 weeks before thefirst administration, or attenuated live vaccine inoculation was planned during thestudy period.

• People with known hypersensitivity to the study drug and excipients;

• Patients diagnosed as active autoimmune diseases within 2 years before the firstadministration;

• Those who participated in and used other anti-tumor clinical trial drugs within 4weeks before the first administration

• Any MF treatment drugs, any immunomodulators, or any immunosuppressants were usedwithin 2 weeks prior to the first dose

• According to the judgment of the investigators, some situations seriously endangerthe safety of the subjects or affect the subjects to complete the study.