Study of TL-895 in Subjects With Myelofibrosis or Indolent Systemic Mastocytosis

A Phase 2 Multicenter Study of TL-895 in Subjects With Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis, Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis, or Indolent Systemic Mastocytosis

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.

Study Overview

• Status: Recruiting
• Conditions: Myelofibrosis; Indolent Systemic Mastocytosis
• Intervention / Treatment: Drug: TL-895; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 121
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: John Mei; Phone Number: 650-542-0136; Email: jmei@teliospharma.com
• Study Contact Backup: Name: Emily Houlihan; Phone Number: 401-954-8042; Email: ehoulihan@teliospharma.com

Study Locations

• Australia
  • East Albury, Australia
    • Completed
    • Border Medical Oncology
  • Kogarah, Australia, 2217
    • Completed
    • Southern Oncology Specialists
  • Perth, Australia, 6000
    • Recruiting
    • Royal Perth Hospital
  • Sydney, Australia, 2010
    • Recruiting
    • St Vincent's Hospital Sydney
• Belgium
  • Liège, Belgium, 4000
    • Recruiting
    • CHU de Liège
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Active, not recruiting
    • Cliniques Universitaires Saint-Luc
• Brazil
  • São Paulo, Brazil, 76805
    • Completed
    • Instituto de Estudos e Pesquisas Sao Lucas - IEP - Sao Lucas
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Completed
    • University Hospital "St Ivan Rilski"
  • Sofia, Bulgaria
    • Active, not recruiting
    • Military Medical Academy
• France
  • Le Mans, France, 72037
    • Active, not recruiting
    • CH Le mans
  • Nantes, France, 44000
    • Completed
    • CHU de Nantes - Hotel-Dieu
  • Nice, France, 06200
    • Completed
    • CHU de Nice - Hopital L' Archet II
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitaetsklinikum Carl Gustav Carus Dresden
  • Düsseldorf, Germany, 40479
    • Completed
    • Marien Hospital Duesseldorf
  • Halle, Germany, 07747
    • Recruiting
    • Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
  • Jena, Germany, 07743
    • Recruiting
    • Universitaetsklinikum Jena
  • Koblenz, Germany, 56073
    • Completed
    • Praxisklinik für Hämatologie und Onkologie
• Hungary
  • Debrecen, Hungary, 4032
    • Completed
    • Debreceni Egyetem Klinikai Kozpont
  • Eger, Hungary, 3300
    • Completed
    • Markhot Ferenc Oktatokorhaz és Rendelointezet
  • Nyíregyháza, Hungary, 4400
    • Completed
    • Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktatókórház Megyei-Városi Tüdőgondozó Intézete
  • Székesfehérvár, Hungary, 8000
    • Completed
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
• Italy
  • Catania, Italy, 95123
    • Active, not recruiting
    • Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
  • Meldola, Italy, 47014
    • Active, not recruiting
    • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
  • Milano, Italy, 20122
    • Active, not recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Milano, Italy, 20162
    • Active, not recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
  • Novara, Italy, 28100
    • Active, not recruiting
    • Azienda Ospedaliero Universitaria Maggiore Della Carita'
  • Perugia, Italy, 06129
    • Active, not recruiting
    • Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
  • Ravenna, Italy, 48121
    • Active, not recruiting
    • AUSL della Romagna-Ospedale S.Maria delle Croci
  • Reggio Calabria, Italy, 89124
    • Active, not recruiting
    • Grande Ospedale Metropolitano Bianchi Melacrino Morelli
  • Roma, Italy, 00161
    • Active, not recruiting
    • Azienda Ospedaliero Universitaria Policlinico Umberto I
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Completed
    • Kyungpook National University Hospital
  • Seoul, Korea, Republic of
    • Completed
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Completed
    • Seoul St. Mary's Hospital, The Catholic University of Korea
• Poland
  • Bydgoszcz, Poland, 85-168
    • Active, not recruiting
    • Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Klinika Hematologi
  • Gdańsk, Poland, 80-211
    • Active, not recruiting
    • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
  • Kraków, Poland, 31-501
    • Not yet recruiting
    • Klinika Hematologii Collegium Medicum Uniwersytetu Jagiellonskiego
  • Wrocław, Poland, 52-007
    • Recruiting
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu, Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
• Spain
  • Barcelona, Spain, 08908
    • Recruiting
    • Institut Catala d'Oncologia - L'Hospitalet
  • Barcelona, Spain, 08916
    • Recruiting
    • Hospital Germans Trias i Pujol
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de octubre
  • Salamanca, Spain, 37007
    • Completed
    • Salamanca University Hospital
  • Zaragoza, Spain, 50006
    • Recruiting
    • Hospital Quironsalud Zaragoza
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Active, not recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
  • Kaohsiung City, Taiwan
    • Completed
    • Chang Gung Memorial Hospital - Kaohsiung Branch
  • Taichung, Taiwan, 404
    • Completed
    • China Medical University Hospital
  • Taipei, Taiwan
    • Completed
    • National Taiwan University Hospital
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Completed
      • University of Colorado - Aurora Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Rochester
  • Ohio
    • Canton, Ohio, United States, 44718
      • Completed
      • Gabrail Cancer Center
    • Cincinnati, Ohio, United States, 45267
      • Active, not recruiting
      • University of Cincinnati (UC) Physicians Company, LLC
    • Columbus, Ohio, United States, 43210
      • Active, not recruiting
      • Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a, Relapsed/Refractory Myelofibrosis; 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 1b, Relapsed/Refractory Myelofibrosis; 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 1c, Relapsed/Refractory Myelofibrosis; 300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 1d, Relapsed/Refractory Myelofibrosis; 450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 2a, JAKi Intolerant Myelofibrosis; 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 2b, JAKi Intolerant Myelofibrosis; 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L; 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L; 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Placebo Comparator: Cohort 5e, Indolent Systemic Mastocytosis; 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.	Drug: Placebo; Placebo to match TL-895
Experimental: Cohort 5a, Indolent Systemic Mastocytosis; 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).	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 5b, Indolent Systemic Mastocytosis; TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 5c, Indolent Systemic Mastocytosis; TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
Experimental: Cohort 5d, Indolent Systemic Mastocytosis; TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.	Drug: TL-895; TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts 1-3: Determine the RP2D of TL-895	The RP2D for Cohorts 1, 2 and 3 will be reported	9 months
Cohort 5: Determine the RP2D of TL-895	The RP2D for Cohort 5 will be reported	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts 1-3: Spleen volume reduction (SVR) rate	The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan (central review).	Week 24
Cohort 5: Changes in patient reported symptoms	Mean change in patient reported symptom assessment	Week 12

Collaborators and Investigators

• Sponsor: Telios Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2020
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplasms, Connective Tissue; Mast Cell Activation Disorders; Primary Myelofibrosis; Mastocytosis; Mastocytosis, Systemic
• Other Study ID Numbers: TL-895-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No