Study of TL-895 in Subjects With Myelofibrosis or Indolent Systemic Mastocytosis
- Conditions
- MyelofibrosisIndolent Systemic Mastocytosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT04655118
- Lead Sponsor
- Telios Pharma, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 121
- 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
- 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 Exclusion Criteria:
- Prior treatment with any BTK or BMX inhibitors
- Prior treatment with Avapritinib, bezuclastinib, or BLU-263/elenestinib
- Diagnosis with another myeloproliferative disorder
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1a, Relapsed/Refractory Myelofibrosis TL-895 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 2a, JAKi Intolerant Myelofibrosis TL-895 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 5e, Indolent Systemic Mastocytosis Placebo Placebo to match TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC. Cohort 1b, Relapsed/Refractory Myelofibrosis TL-895 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle. Cohort 1c, Relapsed/Refractory Myelofibrosis TL-895 300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 1d, Relapsed/Refractory Myelofibrosis TL-895 450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 2b, JAKi Intolerant Myelofibrosis TL-895 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle. Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L TL-895 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 5a, Indolent Systemic Mastocytosis TL-895 TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with best supportive care (BSC). Cohort 5c, Indolent Systemic Mastocytosis TL-895 TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC. Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L TL-895 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle. Cohort 5b, Indolent Systemic Mastocytosis TL-895 TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC. Cohort 5d, Indolent Systemic Mastocytosis TL-895 TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Cohort 5: Changes in patient reported symptoms Week 12 Mean change in patient reported symptom assessment
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).
Trial Locations
- Locations (52)
University of Colorado - Aurora Cancer Center
🇺🇸Aurora, Colorado, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
University of Cincinnati (UC) Physicians Company, LLC
🇺🇸Cincinnati, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Border Medical Oncology
🇦🇺East Albury, Australia
Southern Oncology Specialists
🇦🇺Kogarah, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
St Vincent's Hospital Sydney
🇦🇺Sydney, Australia
Scroll for more (42 remaining)University of Colorado - Aurora Cancer Center🇺🇸Aurora, Colorado, United States