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)
Border Medical Oncology
🇦🇺East Albury, Australia
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Klinika Hematologi
🇵🇱Bydgoszcz, Poland
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Maggiore Della Carita'
🇮🇹Novara, Italy
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
🇮🇹Reggio Calabria, Italy
Instituto de Estudos e Pesquisas Sao Lucas - IEP - Sao Lucas
🇧🇷São Paulo, Brazil
Universitaetsklinikum Jena
🇩🇪Jena, Germany
St Vincent's Hospital Sydney
🇦🇺Sydney, Australia
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Ohio State University
🇺🇸Columbus, Ohio, United States
Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktatókórház Megyei-Városi Tüdőgondozó Intézete
🇭🇺Nyíregyháza, Hungary
Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
🇮🇹Catania, Italy
CH Le Mans
🇫🇷Le Mans, France
Seoul St. Mary's Hospital, The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
CHU de Nantes - Hôtel-Dieu
🇫🇷Nantes, France
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
University Hospital "St Ivan Rilski"
🇧🇬Sofia, Bulgaria
Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
🇨🇳Kaohsiung, Taiwan
Royal Perth Hospital
🇦🇺Perth, Australia
Klinika Hematologii Collegium Medicum Uniwersytetu Jagiellonskiego
🇵🇱Kraków, Poland
Chang Gung Memorial Hospital - Kaohsiung Branch
🇨🇳Kaohsiung City, Taiwan
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
🇮🇹Meldola, Italy
Hospital Quirónsalud Zaragoza
🇪🇸Zaragoza, Spain
Azienda Ospedaliero Universitaria Policlinico Umberto I
🇮🇹Roma, Italy
Marien Hospital Duesseldorf
🇩🇪Düsseldorf, Germany
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Praxisklinik fur Hamatologie und Onkologie
🇩🇪Koblenz, Germany
Southern Oncology Specialists
🇦🇺Kogarah, Australia
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
🇵🇱Gdańsk, Poland
Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
CHU de Nice - Hopital L' Archet II
🇫🇷Nice, France
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Institut Catala d'Oncologia - L'Hospitalet
🇪🇸Barcelona, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Salamanca University Hospital
🇪🇸Salamanca, Spain
University of Colorado - Aurora Cancer Center
🇺🇸Aurora, Colorado, United States
University of Cincinnati (UC) Physicians Company, LLC
🇺🇸Cincinnati, Ohio, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Cliniques Universitaires Saint-Luc
🇧🇪Woluwe-Saint-Lambert, Belgium
Chu De Liège
🇧🇪Liège, Belgium
Military Medical Academy
🇧🇬Sofia, Bulgaria
Universitaetsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Markhot Ferenc Oktatokorhaz es Rendelointezet
🇭🇺Eger, Hungary
Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
🇩🇪Halle, Germany
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Székesfehérvár, Hungary
AUSL della Romagna-Ospedale S.Maria delle Croci
🇮🇹Ravenna, Italy
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu, Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
🇵🇱Wrocław, Poland
China Medical University Hospital
🇨🇳Taichung, Taiwan