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

Myelofibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04655118
• Other study ID #: TL-895-201
• Status: Recruiting
• Phase: Phase 2
• Start date: October 22, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Telios Pharma, Inc.
• Contact: John Mei
• Phone: 650-542-0136
• Email: jmei[@]teliospharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 121
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Indolent Systemic Mastocytosis
• Mastocytosis
• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• TL-895
TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.
• Placebo
Placebo to match TL-895

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Telios Pharma, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Bulgaria,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohorts 1-3: Determine the RP2D of TL-895	The RP2D for Cohorts 1, 2 and 3 will be reported	9 months
Primary	Cohort 5: Determine the RP2D of TL-895	The RP2D for Cohort 5 will be reported	Week 24
Secondary	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
Secondary	Cohort 5: Changes in patient reported symptoms	Mean change in patient reported symptom assessment	Week 12