A Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of TQ05105 Tablets in Subjects With Intermediate/High-risk Myelofibrosis

Korábbi kezelés

• Prior allogeneic stem cell transplantation, or autologous stem cell transplantation within 3 months before first dose, or planned stem cell transplantation.
• Prior treatment with 2 or more Janus kinase (JAK) inhibitors (except Cohort 1).
• Prior splenectomy or splenic radiotherapy within 6 months before first dose.
• Factors affecting oral drug absorption.
• Non-hematologic toxicity from prior therapy not recovered to ≤ grade 1 (excluding hypertension and alopecia).
• Major surgery or significant traumatic injury within 4 weeks before first dose.
• Arterial/venous thrombosis event within 6 months before first dose.
• Newly diagnosed pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before first dose.
• Use of protocol-prohibited myelofibrosis (MF) medications, immunomodulators, or immunosuppressants within specified time before first dose.
• Use of Chinese patent medicines with anti-tumor indications approved by National Medical Products Administration (NMPA) within 2 weeks before first dose.
• Live attenuated vaccine within 4 weeks before first dose or planned during the study.
• Participation in another interventional clinical trial with investigational drug within 4 weeks before first dose.

Más betegség

• Other malignancies within 3 years before first dose or currently present (exceptions per protocol).
• Congenital bleeding or coagulation disorders.
• History of substance abuse or mental disorder.
• Active or uncontrolled severe infection.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Uncontrolled hypertension despite standard therapy.
• Renal failure requiring hemodialysis or peritoneal dialysis.
• History of immunodeficiency or organ transplantation.
• Epilepsy requiring treatment.
• Known hypersensitivity to study drug or excipients.
• Diagnosis of active autoimmune disease within 2 years before first dose.
• Any condition that, in the investigator's judgment, seriously endangers subject safety or interferes with study completion.

Laborértékek

• Grade ≥2 myocardial ischemia or infarction, arrhythmia, QT prolongation, or grade ≥2 congestive heart failure.

Egyéb

• Uncontrolled pleural effusion, pericardial effusion, or ascites.

• Voluntary and signed informed consent, good compliance.
• Age ≥18 years (at time of signing informed consent); Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2; life expectancy ≥24 weeks.
• Diagnosis of primary myelofibrosis (PMF) per World Health Organization (WHO) 2016, or post-polycythemia vera myelofibrosis (post-PV-MF) or post-essential thrombocythemia myelofibrosis (post-ET-MF) per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria; Janus kinase 2 (JAK2) mutation status not restricted.
• Intermediate or high risk per Dynamic International Prognostic Scoring System (DIPSS).
• Cohort 1: Renal function classified as normal, mild impairment, or moderate impairment. Cohort 2: Prior Janus kinase (JAK) inhibitor therapy with refractory, relapsed, or intolerant.
• Spleen enlargement (except Cohort 1).
• Peripheral blood and bone marrow blasts ≤10%.
• No growth factors, colony-stimulating factors, thrombopoietin, or platelet transfusion within 2 weeks before first dose; and routine blood parameters meet requirements within 7 days before first dose.
• Adequate major organ function within 7 days before first dose per protocol (renal function not restricted for Cohort 1).
• Agreement to use effective contraception during the study and for 6 months after; negative pregnancy test for females of childbearing potential; non-lactating.