Myelofibrosis, Primary Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis
Conditions
Keywords
Myelofibrosis
Brief summary
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.
Interventions
DRUGTL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
DRUGRuxolitinib
Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
Sponsors
Telios Pharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib | 28 days | Dose-limiting toxicities (DLTs) will be used to establish the maximum-tolerated dose (MTD) of TL-895 in combination with ruxolitinib. The safety review committee (SRC) will determine the RP2D based on safety and efficacy data of the combination of TL-895 and ruxolitinib. |
| Phase 2 - Spleen Volume Reduction (SVR) at Week 24 | 24 Weeks | The proportion of subjects achieving SVR of ≥35% at Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 - TSS reduction at Week 24 | 24 Weeks | The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by MFSAF v4.0. |
| DOR Spleen | 48 Months | Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death |
| Phase 1b - Spleen Volume Reduction (SVR) at Week 24 | 24 Weeks | The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan. |
| Overall Survival | 48 Months | Time from first dose to death from any cause |
| Progression Free Survival | 48 Month | Time from first dose to progression or death from any cause. |
| Phase 1b - TSS reduction at Week 24 | 24 Weeks | The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. |
Countries
France, Germany, Italy, Poland, Spain, United States
Contacts
Primary ContactJohn Mei
Backup ContactNikki Stuart
Outcome results
None listed