This is an open-label, single-arm, multi-center phase II study consisting of two cohorts. Cohort 1 evaluates the pharmacokinetics (PK) of TQ05105 in myelofibrosis participants with normal, mild, or moderate renal impairment to guide dosing. Cohort 2 evaluates the efficacy and safety of TQ05105 in participants with intermediate/high-risk myelofibrosis who are refractory, relapsed, or intolerant to prior Janus kinase (JAK) inhibitor therapy.

Inclusion Criteria:

1. Voluntary and signed informed consent, good compliance.
2. Age ≥18 years (at time of signing informed consent); Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2; life expectancy ≥24 weeks.
3. 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.
4. Intermediate or high risk per Dynamic International Prognostic Scoring System (DIPSS).
5. 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.
6. Spleen enlargement (except Cohort 1).
7. Peripheral blood and bone marrow blasts ≤10%.
8. 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.
9. Adequate major organ function within 7 days before first dose per protocol (renal function not restricted for Cohort 1).
10. Agreement to use effective contraception during the study and for 6 months after; negative pregnancy test for females of childbearing potential; non-lactating.

Exclusion Criteria:

1. Prior allogeneic stem cell transplantation, or autologous stem cell transplantation within 3 months before first dose, or planned stem cell transplantation.
2. Prior treatment with 2 or more Janus kinase (JAK) inhibitors (except Cohort 1).
3. Prior splenectomy or splenic radiotherapy within 6 months before first dose.
4. Other malignancies within 3 years before first dose or currently present (exceptions per protocol).
5. Factors affecting oral drug absorption.
6. Non-hematologic toxicity from prior therapy not recovered to ≤ grade 1 (excluding hypertension and alopecia).
7. Major surgery or significant traumatic injury within 4 weeks before first dose.
8. Congenital bleeding or coagulation disorders.
9. Arterial/venous thrombosis event within 6 months before first dose.
10. History of substance abuse or mental disorder.
11. Active or uncontrolled severe infection.
12. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
13. Grade ≥2 myocardial ischemia or infarction, arrhythmia, QT prolongation, or grade ≥2 congestive heart failure.
14. Uncontrolled hypertension despite standard therapy.
15. Renal failure requiring hemodialysis or peritoneal dialysis.
16. Newly diagnosed pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before first dose.
17. History of immunodeficiency or organ transplantation.
18. Epilepsy requiring treatment.
19. Use of protocol-prohibited myelofibrosis (MF) medications, immunomodulators, or immunosuppressants within specified time before first dose.
20. Use of Chinese patent medicines with anti-tumor indications approved by National Medical Products Administration (NMPA) within 2 weeks before first dose.
21. Uncontrolled pleural effusion, pericardial effusion, or ascites.
22. Live attenuated vaccine within 4 weeks before first dose or planned during the study.
23. Known hypersensitivity to study drug or excipients.
24. Diagnosis of active autoimmune disease within 2 years before first dose.
25. Participation in another interventional clinical trial with investigational drug within 4 weeks before first dose.
26. Any condition that, in the investigator's judgment, seriously endangers subject safety or interferes with study completion.