Overview
This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis. Participants must have MF (PMF, Post PV MF, or Post ET MF) who are JAKi treatment-naïve or those who have a suboptimal response to ruxolitinib.
Eligibility
Inclusion Criteria:
Subjects with suboptimal response to ruxolitinib:
- Treatment with at a stable dose of ruxolitinib prior to study entry
- Subjects ≥ 18 years of age and able to provide informed consent.
- Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
- High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
- Palpable spleen measuring ≥ 5 cm below the left lower coastal margin (LLCM) or spleen volume of ≥ 450 cm3 by MRI or CT scan assessment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Adequate hematological, hepatic, & renal function.
Exclusion Criteria:
Treatment-naive subjects:
- Prior treatment with any JAKi
Subjects with suboptimal response to ruxolitinib:
- Documented disease progression while on ruxolitinib treatment
All subjects:
- Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
- Prior treatment with a BTK or BMX inhibitor