Phase 2 Study of Flonoltinib Maleate Oral Regimens in Patients With Myelofibrosis

NCT07750574 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: FM-MF-02
• Study Type: interventional
• Target: 105
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn which of three different doses of Flonoltinib Maleate taken by mouth daily works best to treat adult patients with myelofibrosis in whom the most common approved therapy has failed to adequately control the disease. It will also learn about the safety of the three different daily doses of Flonoltinib Maleate. The main questions it aims to answer are: Which dose is the best at controlling the symptoms and signs of organ damage caused by myelofibrosis? What medical problems do participants have when taking the three different doses of Flonoltinib Maleate? Researchers will compare the three different doses of Flonoltinib Maleate to see which dose is best to treat patients with myelofibrosis. Participants will: Take Flonoltinib Maleate every day for as long as it seems to be of benefit to them in terms of controlling myelofibrosis. Visit the clinic for checkups and tests after giving fully informed written consent confirming that they would like to consider entering the study. Visit the clinic for checkups and tests when on the study once every 2 weeks for the first 2 months, every 4 weeks after that, and when coming off study therapy. Keep a diary of their symptoms.

Conditions

Myelofibrosis; Myelofibrosis Due to and Following Polycythemia Vera; Myelofibrosis Transformation in Essential Thrombocythemia; Myelofibrosis With High Molecular Risk Mutations; Myelofibrosis With Myeloid Metaplasia; Myelofibrosis, Post ET; Myelofibrosis, Post PV; Myelofibrosis, Primary; Myelofibrosis; Anemia; Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Myelofibrosis，MF; Myelofibrosis (PMF)

Keywords

Myelofibrosis. JAK inhibitor therapy. De-novo diagnosis. Prior JAK inhibitor therapy. Novel JAK inhibitor. JAK2. FLT3. CDK6.

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with ≥35% reduction in spleen volume as assessed by imaging from baseline to week 24

  The spleen volume as measured by a CT or MRI scan before study therapy commences will be compared with the spleen volume as measured by the same method as used at baseline. The percentage of participants who show a 35% or more reduction in spleen volume will be calculated.

  Baseline and at 24 weeks on study

Secondary Outcomes (15)

• Percentage of participants achieving a TSS50, as measured by the MFSAF v4.0 at week 24.

  Baseline and at 24 weeks on study

• Absolute mean change in TSS from baseline to weeks 12 and 24 as measured by MFSAF V4.0

  Baseline and at 12 weeks and 24 weeks on study

• Absolute mean change in TSS excluding fatigue from baseline to weeks 12 and 24

  Baseline, at weeks 12 and 24 on study

• Percentage of patients achieving SVR35 from baseline to week 12 (IRC and investigator)

  Baseline and at week 12 on study.

• Percentage of patients with SVR35 from baseline to Week 24 (investigator

  Baseline and at 24 weeks on study

Study Arms (3)

35 fully evaluable patients (14 JAKi-naïve - 21 JAKi-resistant) will receive Flonoltinib 50mg daily

EXPERIMENTAL

This study arm will include 35 fully eligible and evaluable participants with myelofibrosis, including 14 JAKi-naïve and 63 JAKi-resistant, who are randomized to receive 50mg of oral Flonoltinib daily. Participants will receive continuous treatment until unacceptable toxicities, progressive disease or meeting other stopping criteria. The key safety endpoints and clinical efficacy endpoints will be evaluated at the end of 6 cycles (24 weeks). Other efficacy and safety evaluations will be conducted every 3 to 6 cycles. Safety follow-up will be conducted up to 30 days after the last dose and all participants will be followed up for adverse events, serious adverse events, and concomitant medication (including any new therapy) for 30 days following last Flonoltinib dose.

Drug: Flonoltinib Maleate orally

35 participants (14 JAKi-naïve, 21 JAKi-resistant) with MF will receive Flonoltinib 75mg daily

EXPERIMENTAL

This study arm will include 35 fully eligible and evaluable participants with myelofibrosis, including 14 JAKi-naïve and 63 JAKi-resistant, who are randomized to receive 75mg of oral Flonoltinib daily. Participants will receive continuous treatment until unacceptable toxicities, progressive disease or meeting other stopping criteria. The key safety endpoints and clinical efficacy endpoints will be evaluated at the end of 6 cycles (24 weeks). Other efficacy and safety evaluations will be conducted every 3 to 6 cycles. Safety follow-up will be conducted up to 30 days after the last dose and all participants will be followed up for adverse events, serious adverse events, and concomitant medication (including any new therapy) for 30 days following last Flonoltinib dose.

Drug: Flonoltinib Maleate orally

35 fully evaluable patients (14 JAKi-naïve - 21 JAKi-resistant) will receive Flonoltinib 100mg daily

EXPERIMENTAL

This study arm will include 35 fully eligible and evaluable participants with myelofibrosis, including 14 JAKi-naïve and 63 JAKi-resistant, who are randomized to receive 100mg of oral Flonoltinib daily. Participants will receive continuous treatment until unacceptable toxicities, progressive disease or meeting other stopping criteria. The key safety endpoints and clinical efficacy endpoints will be evaluated at the end of 6 cycles (24 weeks). Other efficacy and safety evaluations will be conducted every 3 to 6 cycles. Safety follow-up will be conducted up to 30 days after the last dose and all participants will be followed up for adverse events, serious adverse events, and concomitant medication (including any new therapy) for 30 days following last Flonoltinib dose.

Drug: Flonoltinib Maleate orally

Interventions

Flonoltinib Maleate orally DRUG

Dose of Flonoltinib Maleate will be 50mg daily

35 fully evaluable patients (14 JAKi-naïve - 21 JAKi-resistant) will receive Flonoltinib 50mg daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must:
• Have signed the current relevant ICF prior to any study related procedures;
• Understand and commit to comply with study requirements;
• Be ≥18 years of age;
• Be able to swallow and retain oral medications;
• Be diagnosed with PMF according to the 2016 WHO criteria, or PPV-MF or PET-MF according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria;
• Have Intermediate-1 to high-risk myelofibrosis (as per Dynamic International Prognostic Scoring System \[DIPSS\] risk categories) and be either JAKi-naïve or JAKi-resistant. JAKi-naïve patients include those with JAKi exposure of no more than 14 days. The JAKi-resistant patients need to meet 1 of the following criteria: a) Treatment with JAKi for 3 months with inadequate efficacy response defined as \< 10% spleen volume reduction (SVR) by Magnetic Resonance Imaging (MRI) or \<30% decrease from baseline in spleen size by palpation or regrowth to these parameters following an initial response; b) Treatment with JAKi for ≥28 days complicated by any of the following: development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) or cytopenia-related intolerance requiring ≥2 dose reductions or discontinuation of a JAKi; c) Persistent MF-related symptoms defined as less than 50% reduction in TSS (MFSAF V 4.0) after 3 months of JAKi therapy;
• Not be intended to undergo stem cell transplantation for at least 6 months;
• Have life expectancy per investigator assessment ≥ 12 weeks;
• Have Eastern Cooperative Oncology Group (ECOG) score ≤ 2;
• Have splenomegaly: palpable spleen extending at least 5 cm below the costal margin or unpalpable due to body habitus (obesity), but confirmed to be ≥450 cm³ by MRI (or computed tomography \[CT\] scan) at screening;
• Have at least 2 symptoms with an average score ≥3 over the 7-day period prior to randomization or an average total score of ≥10 over the 7-day period prior to randomization using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0;
• Have bone marrow blast cells ≤10% and peripheral blood blast cells ≤10%;
• Have PLT ≥50 × 109 /L and absolute neutrophil count (ANC) ≥ 1.0 × 109 /L and hemoglobin (HGB) \>60 g/L without the assistance of CSF, EPO, TPO, or component blood transfusions. Have discontinued growth factors and platelets transfusions for more than 2 weeks before screening tests;
• Have no overt significant disease involving heart, lungs, liver, kidneys, or pancreas (left ventricular ejection fraction ≥ 45%; serum direct bilirubin ≤2 × upper limit of normal \[ULN\]; serum creatinine ≤1.5 × ULN or Estimated Glomerular Filtration Rate \[eGFR\] by the 2021 chronic kidney disease-Epidemiology Collaboration formula ≥ 45 mL/min/1.73 m2; alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\] ≤2.5 × ULN) or ≤5 × ULN if associated with liver MF involvement;

You may not qualify if:

• Participants must not:
• Have failure to recover from toxic effects of prior anticancer therapy to Grade 1 or below (except alopecia), or failure to fully recover from prior surgery (major surgery within 4 weeks);
• Have known hypersensitivity to the investigational product or its excipients;
• Have any significant clinical or laboratory abnormality that would interfere with accurate safety evaluation on study, including:
• Uncontrolled diabetes with fasting blood glucose \>250 mg/dL (13.9 mmol/L);
• Hypertension not controlled by one or two antihypertensive drugs to the following range: systolic \<160 mmHg, diastolic \<100 mmHg;
• Peripheral neuropathy of Grade 2 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) v6.0;
• Thyroid dysfunction of Grade 2 or higher per CTCAE v6.0;
• Any other relevant abnormality in the opinion of the investigator;
• Have a history of congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism within the 6 months prior to screening;
• Have impaired cardiac function including any of the following conditions as determined by echocardiogram or electrocardiogram (ECG): left ventricular ejection fraction less than 45%, or complete left bundle branch block with ST-segment depression greater than 1 mm or T-wave inversion across 2 or more leads. Other criteria include congenital ventricular arrhythmias, clinically significant tachycardia (greater than 100 beats per minute), bradycardia (less than 50 beats per minute) with accompanying clinical symptoms, heart rate less than 60 beats per minute with symptoms, an ECG Corrected QT Interval (QTc) interval greater than 450 ms, or clinically significant cardiac conditions such as unstable angina, congestive heart failure, or myocardial infarction occurring within the last 6 months. Patients with heart failure who meet New York Heart Association class III and IV definitions are ineligible for this study;
• Have an active serious infection requiring treatment at the time of screening;
• Have undergone splenectomy or who have received splenic irradiation within 6 months prior to screening;
• Have Human Immunodeficiency Virus (HIV) positive, active Hepatitis B (Hepatitis B Surface Antigen \[HBsAg\] positive and Hepatitis B Virus \[HBV\]-DNA ≥1000 copies/mL), or positive for Hepatitis C Virus (HCV) antibodies or HCV-RNA at screening;
• Have epilepsy or are taking psychotropic or sedative medications at screening;

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Related Publications (9)

• Harrison CN, Schaap N, Mesa RA. Management of myelofibrosis after ruxolitinib failure. Ann Hematol. 2020 Jun;99(6):1177-1191. doi: 10.1007/s00277-020-04002-9. Epub 2020 Mar 20.

  PMID: 32198525 BACKGROUND

• Stuckey R, Segura Diaz A, Gomez-Casares MT. Myelofibrosis: Treatment Options After Ruxolitinib Failure. Curr Oncol. 2025 Jun 9;32(6):339. doi: 10.3390/curroncol32060339.

  PMID: 40558282 BACKGROUND

• Hu M, Yang T, Yang L, Niu L, Zhu J, Zhao A, Shi M, Yuan X, Tang M, Yang J, Pei H, Yang Z, Chen Q, Ye H, Niu T, Chen L. Preclinical studies of Flonoltinib Maleate, a novel JAK2/FLT3 inhibitor, in treatment of JAK2V617F-induced myeloproliferative neoplasms. Blood Cancer J. 2022 Mar 7;12(3):37. doi: 10.1038/s41408-022-00628-2.

  PMID: 35256594 BACKGROUND

• Ipek Y, Kilic B, Gunay UB, Eskazan AE. Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis. Expert Opin Investig Drugs. 2023 Jul-Dec;32(10):931-940. doi: 10.1080/13543784.2023.2269078. Epub 2023 Nov 6.

  PMID: 37811861 BACKGROUND

• Hu M, Yang T, Yang L, Niu L, Zhu J, Zhao A, Shi M, Yuan X, Tang M, Yang J, Pei H, Yang Z, Chen Q, Ye H, Niu T, Chen L. Correction to: Preclinical studies of Flonoltinib Maleate, a novel JAK2/FLT3 inhibitor, in treatment of JAK2V617F-induced myeloproliferative neoplasms. Blood Cancer J. 2024 Jun 26;14(1):104. doi: 10.1038/s41408-024-01058-y. No abstract available.

  PMID: 38926354 BACKGROUND

• Ma Z, Tang M, Pu Q, Wei P, Wu R, Zhao J, Zhou Y, Yang Z, Ye H, Chen L. UPLC-MS/MS method development and application to pharmacokinetic study in rats and dogs of Flonoltinib Maleat. J Chromatogr B Analyt Technol Biomed Life Sci. 2023 May 15;1223:123696. doi: 10.1016/j.jchromb.2023.123696. Epub 2023 Apr 15.

  PMID: 37086507 BACKGROUND

• Ma Z, Tang M, Chen L. Study on tissue distribution, metabolite profiling, and excretion of [14C]-labeled flonoltinib maleate in rats. J Pharm Biomed Anal. 2024 Apr 15;241:115984. doi: 10.1016/j.jpba.2024.115984. Epub 2024 Jan 15.

  PMID: 38266453 BACKGROUND

• Zhu J, Yang T, Tang M, Yang Z, Pei H, Ye H, Tang Y, Cheng Z, Lin P, Chen L. Studies on the anti-psoriasis effects and its mechanism of a dual JAK2/FLT3 inhibitor flonoltinib maleate. Biomed Pharmacother. 2021 May;137:111373. doi: 10.1016/j.biopha.2021.111373. Epub 2021 Feb 24.

  PMID: 33761599 BACKGROUND

• Yang L, Tan K, Liang R, Zhang W, Wang Y, Chen L. Assessment of flonoltinib maleate versus ruxolitinib phosphate in intermediate- to high-risk myelofibrosis (FMF-02): study protocol for a multicenter, randomized, open-label phase IIB trial. Ther Adv Hematol. 2026 Mar 19;17:20406207261424845. doi: 10.1177/20406207261424845. eCollection 2026.

  PMID: 41883618 BACKGROUND

Related Links

• Sponsor website

MeSH Terms

Conditions

Primary Myelofibrosis; Anemia

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Francis J Giles, MD

CONTACT

281-796-1852; frank.giles@zenitar.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized at time of study entry to one of three cohorts - each cohort will receive a different dose of the investigation agent

Study Record Dates

• First Submitted: August 2, 2026
• First Posted: August 6, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: August 6, 2026

Record last verified: 2026-08