This is a Phase I clinical study to evaluate the safety and tolerability, pharmacokinetic characteristics and preliminary efficacy of oral WJ01024 administered as monotherapy and in combination with ruxolitinib in patients with myelofibrosis（MF）. The study will be conducted in two phases: Phase IA and Phase IB.
Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant). Phase IB is a dose-escalation and dose-expansion study of WJ01024 in combination with ruxolitinib in JAKi-naïve patients with intermediate- or high-risk MF.
The subjects voluntarily participated in this study after obtaining full informed consent and signed the informed consent form.
Age ≥18 years old, gender not limited;
Patients diagnosed with primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or patients diagnosed with post-essential thrombocythemia MF (PET-MF) or post-polycythemia vera MF (PPV-MF) according to International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria;
Patients evaluated as intermediate-1, intermediate-2, or high-risk according to the International Prognostic System (DIPSS) scoring system;;
Peripheral blood blasts >5% or Bone marrow blasts >10%.
Previous treatment with XPO1 inhibitors.
Unable to cooperate with or unable to perform MRI or CT scans as deemed necessary by sponsor and investigator
Treatment with strong CYP3A inhibitors or inducers within 14 days prior to initial administration"
Single group
WJ01024 tablet
Drug5-20mg BID (dosage per investigator judgement)
DLT
Incidence of DLT
AE
incidence and severity of adverse events(AEs) and serious adverse events(SAEs),as well as abnormal changes in clinical significance laboratory tests and other examinations
MTD
Evaluate the Maximum tolerated dose
RP2D
Evaluate the recommended dose for phase II
Pharmacokinetic (PK) Parameter
The blood concentration of WJ01024
SVR35
Percentage of subjects with spleen volume reduction of ≥35% (SVR35)
Score in MPN-SAF-TSS
Percentage reduction in Total Symptom Score(TSS) and proportion of subjects achieving ≥50% reduction (TSS50) assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
incidence and severity of adverse events and serious adverse events
incidence and severity of adverse events nd serious adverse events,as well as abnormal changes in clinical significance laboratory tests and other examinations
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