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

NCT04655118 | Recruiting Phase 2 FDA Drug

• 1 other identifier: TL-895-201
• Study Type: interventional
• Target: 121
• Locations: 13 countries
• Sites: 52

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.

Conditions

Myelofibrosis; Indolent Systemic Mastocytosis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Cohorts 1-3: Spleen volume reduction (SVR) rate

  Week 24

• Cohort 5: Changes in patient reported symptoms

  Week 12

Study Arms (13)

Cohort 1a, Relapsed/Refractory Myelofibrosis

EXPERIMENTAL

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

Cohort 1b, Relapsed/Refractory Myelofibrosis

EXPERIMENTAL

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

Cohort 1c, Relapsed/Refractory Myelofibrosis

EXPERIMENTAL

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

Cohort 1d, Relapsed/Refractory Myelofibrosis

EXPERIMENTAL

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

Cohort 2a, JAKi Intolerant Myelofibrosis

EXPERIMENTAL

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

Cohort 2b, JAKi Intolerant Myelofibrosis

EXPERIMENTAL

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

Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L

EXPERIMENTAL

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

Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L

EXPERIMENTAL

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

Cohort 5a, Indolent Systemic Mastocytosis

EXPERIMENTAL

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

Cohort 5b, Indolent Systemic Mastocytosis

EXPERIMENTAL

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

Cohort 5c, Indolent Systemic Mastocytosis

EXPERIMENTAL

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

Cohort 5d, Indolent Systemic Mastocytosis

EXPERIMENTAL

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

Cohort 5e, Indolent Systemic Mastocytosis

PLACEBO COMPARATOR

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

Interventions

TL-895 DRUG

TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.

Cohort 1a, Relapsed/Refractory Myelofibrosis; Cohort 1b, Relapsed/Refractory Myelofibrosis; Cohort 1c, Relapsed/Refractory Myelofibrosis; Cohort 1d, Relapsed/Refractory Myelofibrosis; Cohort 2a, JAKi Intolerant Myelofibrosis; Cohort 2b, JAKi Intolerant Myelofibrosis; Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L; Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L; Cohort 5a, Indolent Systemic Mastocytosis; Cohort 5b, Indolent Systemic Mastocytosis; Cohort 5c, Indolent Systemic Mastocytosis; Cohort 5d, Indolent Systemic Mastocytosis

Placebo DRUG

Placebo to match TL-895

Cohort 5e, Indolent Systemic Mastocytosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• Prior treatment with any BTK or BMX inhibitors
• Prior treatment with Avapritinib, bezuclastinib, or BLU-263/elenestinib
• Diagnosis with another myeloproliferative disorder

Sponsors & Collaborators

• Telios Pharma, Inc.: lead

Study Sites (52)

University of Colorado - Aurora Cancer Center

Aurora, Colorado, 80045, United States

COMPLETED

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

COMPLETED

University of Cincinnati (UC) Physicians Company, LLC

Cincinnati, Ohio, 45267, United States

ACTIVE NOT RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

ACTIVE NOT RECRUITING

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Border Medical Oncology

East Albury, Australia

COMPLETED

Southern Oncology Specialists

Kogarah, 2217, Australia

COMPLETED

Royal Perth Hospital

Perth, 6000, Australia

RECRUITING

St Vincent's Hospital Sydney

Sydney, 2010, Australia

RECRUITING

Chu De Liège

Liège, 4000, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, 1200, Belgium

ACTIVE NOT RECRUITING

Instituto de Estudos e Pesquisas Sao Lucas - IEP - Sao Lucas

São Paulo, 76805, Brazil

COMPLETED

University Hospital "St Ivan Rilski"

Sofia, 1431, Bulgaria

COMPLETED

Military Medical Academy

Sofia, Bulgaria

ACTIVE NOT RECRUITING

CH Le Mans

Le Mans, 72037, France

ACTIVE NOT RECRUITING

CHU de Nantes - Hôtel-Dieu

Nantes, 44000, France

COMPLETED

CHU de Nice - Hopital L' Archet II

Nice, 06200, France

COMPLETED

Universitaetsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

RECRUITING

Marien Hospital Duesseldorf

Düsseldorf, 40479, Germany

COMPLETED

Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall

Halle, 07747, Germany

RECRUITING

Universitaetsklinikum Jena

Jena, 07743, Germany

RECRUITING

Praxisklinik fur Hamatologie und Onkologie

Koblenz, 56073, Germany

COMPLETED

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

COMPLETED

Markhot Ferenc Oktatokorhaz es Rendelointezet

Eger, 3300, Hungary

COMPLETED

Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktatókórház Megyei-Városi Tüdőgondozó Intézete

Nyíregyháza, 4400, Hungary

COMPLETED

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, 8000, Hungary

COMPLETED

Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico

Catania, 95123, Italy

ACTIVE NOT RECRUITING

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori

Meldola, 47014, Italy

ACTIVE NOT RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

ACTIVE NOT RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero Universitaria Maggiore Della Carita'

Novara, 28100, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia

Perugia, 06129, Italy

ACTIVE NOT RECRUITING

AUSL della Romagna-Ospedale S.Maria delle Croci

Ravenna, 48121, Italy

ACTIVE NOT RECRUITING

Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, 89124, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero Universitaria Policlinico Umberto I

Roma, 00161, Italy

ACTIVE NOT RECRUITING

Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Klinika Hematologi

Bydgoszcz, 85-168, Poland

ACTIVE NOT RECRUITING

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, 80-211, Poland

ACTIVE NOT RECRUITING

Klinika Hematologii Collegium Medicum Uniwersytetu Jagiellonskiego

Krakow, 31-501, Poland

NOT YET RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu, Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku

Wroclaw, 52-007, Poland

RECRUITING

Kyungpook National University Hospital

Daegu, South Korea

COMPLETED

Seoul National University Hospital

Seoul, South Korea

COMPLETED

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, South Korea

COMPLETED

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, 08908, Spain

RECRUITING

Hospital Germans Trias i Pujol

Barcelona, 08916, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Salamanca University Hospital

Salamanca, 37007, Spain

COMPLETED

Hospital Quirónsalud Zaragoza

Zaragoza, 50006, Spain

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)

Kaohsiung City, 80756, Taiwan

ACTIVE NOT RECRUITING

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, Taiwan

COMPLETED

China Medical University Hospital

Taichung, 404, Taiwan

COMPLETED

National Taiwan University Hospital

Taipei, Taiwan

COMPLETED

MeSH Terms

Conditions

Primary Myelofibrosis; Mastocytosis, Systemic

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases

Central Study Contacts

John Mei

CONTACT

650-542-0136; jmei@teliospharma.com

Emily Houlihan

CONTACT

401-954-8042; ehoulihan@teliospharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 7, 2020
• Study Start: October 22, 2020
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: May 10, 2024

Record last verified: 2024-05

Locations

BU (2); PL (4); AU (4); BE (2); KR (3); ES (5); TW (4); US (6); BR (1); FR (3); HU (4); DE (5); IT (9)