a clinical trial of tq05105 tablets combined with tqb3617 capsules in the treatment of myelofibrosis (mf)

Conditions: Myelofibrosis

Summary: this is an open, single-arm, multi-center clinical study designed to evaluate the efficacy and safety of tq05105 tablets combined with tqb3617 capsules in patients with intermediate- and high-risk myelofibrosis.


Eligibility criteria:
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.