Treatment of Myelofibrosis with TQ05105 and TQB3617

Inclusion Criteria:

* Voluntary and signed informed consent, good compliance.
* Age: 18 or above (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.
* Within 7 days before the first administration, the symptom score of myeloproliferative neoplasms should meet certain requirements.
* Patients with poor efficacy of JAK inhibitors (for phase Ib and phase II cohort 2, cohort 3)
* Patients who had not received JAK inhibitor treatment (for phase II cohort 1).
* 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 BET inhibitors combined with JAK inhibitor;
* Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
* Use of any MF medications, any immunomodulators, any immunosuppressive agents, within 2 weeks prior to first administration (There are separate withdrawal requirements for hydroxyurea, JAK inhibitors, androgen drugs, erythropoietin, long-acting recombinant interferon-α, etc.);
* 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;
* 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, or active Corona Virus Disease 2019 (COVID-19) infection;
* Patients with grade III or above congestive heart failure, unstable angina pectoris or myocardial infarction, or arrhythmia requiring treatment, or QT interval prolongation 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-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;
* 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 (except JAK inhibitor-related clinical trials).
* According to the judgment of the investigators, some situations seriously endanger the safety of the subjects or affect the subjects to complete the study.