Myelofibrosis, Indolent Systemic Mastocytosis
Conditions
Brief summary
This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis (Cohorts 1-3) or Indolent Systemic Mastocytosis (Cohort 5). Participants must be diagnosed with Myelofibrosis and be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment, or be diagnosed with Indolent Systemic Mastocytosis.
Interventions
DRUGTL-895
TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
DRUGPlacebo
Placebo to match TL-895
Sponsors
Telios Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohorts 1-3 Key Inclusion Criteria: * Adults ≥18 years of age * Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria * Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 * Adequate hematologic, hepatic, and renal functions * MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 for each of the 2 symptoms per MFSAF v4.0 * Cohort 3 only: Ineligibility for JAKi treatment with a platelet count of ≥ 25 and \< 50 x 10\^9/L Key
Exclusion criteria
* Prior treatment with any BTK or BMX inhibitors * Prior treatment with JAKi within 28 days prior to study treatment * Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment Cohort 5 Key Inclusion Criteria: * Adults ≥18 years of age * Confirmed diagnosis of ISM as defined by WHO diagnostic criteria based on review of bone marrow biopsy pathology report results * Subject must have moderate-to-severe symptoms Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1-3: Determine the RP2D of TL-895 | 9 months | The RP2D for Cohorts 1, 2 and 3 will be reported |
| Cohort 5: Determine the RP2D of TL-895 | Week 24 | The RP2D for Cohort 5 will be reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1-3: Spleen volume reduction (SVR) rate | Week 24 | The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan (central review). |
| Cohort 5: Changes in patient reported symptoms | Week 12 | Mean change in patient reported symptom assessment |
Countries
Australia, Belgium, Brazil, Bulgaria, France, Germany, Hungary, Italy, Poland, South Korea, Spain, Taiwan, United States
Contacts
Primary ContactJohn Mei
Backup ContactEmily Houlihan
Outcome results
None listed