A Phase II Clinical Trial of Flonoltinib Maleate Tablet in Intermediate-High Risk Myelofibrosis

Inclusion Criteria:

1. Age ≥ 18 years, no gender restrictions;

2. Diagnosed with primary myelofibrosis (PMF) according to WHO criteria (2016 edition)or post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemiamyelofibrosis (PET-MF) according to IWG-MRT criteria;

3. Evaluated as intermediate-2 or high-risk myelofibrosis according to the DynamicInternational Prognostic Scoring System (DIPSS) risk classification;

4. Expected survival ≥ 24 weeks;

5. ECOG score of 0-2;

6. Splenomegaly: palpable spleen edge reaching or exceeding 5 cm below the costalmargin (distance from the intersection of the left midclavicular line and the leftcostal margin to the farthest point of the spleen); or not palpable due to bodyhabitus (obesity) but confirmed by magnetic resonance imaging (MRI ) (or CT scan ifnecessary) at screening with spleen volume ≥ 450 cm³;

7. Blasts in peripheral blood and bone marrow ≤ 10%; 8) Within 7 days before the firstdose, absolute absolute neutrophil count (ANC )≥ 1.0×10^9/L, platelet count ≥ 50×10^9/L, hemoglobin (HGB )> 60 g/L (participants should not have received growthfactors, colony-stimulating factors, thrombopoietic agents, or platelet transfusionswithin 2 weeks before the baseline assessment prior to the first dose); 9) Majororgan function basically normal within 7 days before the first dose; 10) Able tounderstand and voluntarily sign the informed consent form.

Exclusion Criteria:

1. Previous anticancer treatment-related toxic reactions have not recovered to grade 1or below (excluding alopecia and conditions specified in inclusion criteria 8 and 9), or have not fully recovered from previous surgery (major surgery within 4weeks);

2. Hypersensitivity, allergic to the investigational drug or its excipients;

3. Previous intolerance or resistance to ruxolitinib;

4. Use of JAK inhibitors within 4 weeks before the first dose;

5. Any significant clinical and laboratory abnormalities that, in the investigator'sopinion, affect safety evaluation;

6. History of congestive heart failure, unstable angina, myocardial infarction,cerebrovascular accident (excluding lacunar infarction), or pulmonary embolismwithin 6 months prior to screening;

7. Impaired cardiac function or arrhythmic disease requiring treatment at screening;

8. Any active infection requiring intravenous antibiotic treatment at screening;

9. Active tuberculosis infection within 48 weeks prior to screening or latenttuberculosis infection indicated by tuberculosis-related tests during the screeningperiod;

10. Patients who have undergone splenectomy or received radiation therapy to the spleenarea within 12 months before the first dose;

11. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, except for: a)HBV infection: Patients with positive hepatitis B surface antigen (HbsAg) orhepatitis B core antibody (HbcAb) with undetectable peripheral blood HBV-DNA (belowthe detection limit of the testing laboratory) can be enrolled; they must continueantiviral therapy and have HBV-DNA testing every 12 weeks and at the end oftreatment (EOT); b) HCV seropositive patients with negative HCV RNA can be enrolled.

12. Positive for human immunodeficiency virus antibody (HIV-Ab) or Treponema pallidumantibody (TP-Ab) (patients with positive Treponema pallidum antibody can have atiter test, and the investigator will determine eligibility based on comprehensivejudgment);

13. Patients with epilepsy or those using psychiatric drugs or sedatives at screening (excluding those used for sleep purposes);

14. Pregnant or breastfeeding women, and patients with reproductive potential (male andfemale) who refuse to use contraceptive measures during the trial and for 6 monthsafter the trial;

15. Patients who have had another malignancy within 5 years before the first dose (excluding cured in-situ carcinoma and basal cell carcinoma of the skin);

16. Patients with other severe diseases that, in the investigator's opinion, may affectsafety or compliance;

17. Patients who participated in other clinical trials of investigational drugs ormedical devices within 1 month before the first dose and used the investigationaldrug or device;

18. Use of any treatment for MF (other than JAK inhibitors) within 2 weeks or 5half-lives (whichever is longer) before the first dose, any immunomodulatory agents (e.g., thalidomide), any immunosuppressants, ≥10 mg/day prednisone or equivalentbiological potency corticosteroids, or growth factors (e.g., erythropoietin (EPO)) (Traditional Chinese medicine should be stopped 1 day before the first dose);

19. Patients with a history of congenital or acquired bleeding disorders;

20. Other factors that the investigator deems unsuitable for participation in the trial.