Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib

Myelofibrosis Clinical Trial

Official title:

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of TL-895 Combined With Ruxolitinib in Janus-associated Kinase Inhibitor (JAKi) Treatment-Naïve Myelofibrosis (MF) Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05280509
• Other study ID #: TL-895-209
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 9, 2022
• Est. completion date: April 2027

Study information

• Verified date: February 2023
• 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. Participants must have MF (PMF, Post PV MF, or Post ET MF) who are JAKi treatment-naïve or those who have a suboptimal response to ruxolitinib.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: April 2027
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects with suboptimal response to ruxolitinib:

• Treatment with at a stable dose of ruxolitinib prior to study entry
• Subjects = 18 years of age and able to provide informed consent.
• Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
• High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
• Palpable spleen measuring = 5 cm below the left lower coastal margin (LLCM) or spleen volume of = 450 cm3 by MRI or CT scan assessment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Adequate hematological, hepatic, & renal function. Exclusion Criteria:

Treatment-naive subjects:

• Prior treatment with any JAKi

Subjects with suboptimal response to ruxolitinib:

• Documented disease progression while on ruxolitinib treatment

All subjects:

• Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
• Prior treatment with a BTK or BMX inhibitor

Related Conditions & MeSH terms

• Myelofibrosis
• Post-ET Myelofibrosis
• Post-PV MF
• Primary Myelofibrosis

Intervention

Drug:
• TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
• Ruxolitinib
Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	AP-HM - Hôpital de la Timone	Marseille
France	CHU de Nice - Hopital L'Archet II	Nice
France	Hôpital Saint Louis - AP-HP	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
Germany	Marien Hospital Duesseldorf	Düsseldorf
Germany	Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall	Halle
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola	Bologna
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milano
Italy	Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia	Perugia
Poland	Pratia Onkologia Katowice	Katowice
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Quironsalud de Zaragoza	Zaragoza
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Gabrail Cancer Center	Canton	Ohio
United States	University of Cincinnati (UC)	Cincinnati	Ohio
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Telios Pharma, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib	Dose-limiting toxicities (DLTs) will be used to establish the maximum-tolerated dose (MTD) of TL-895 in combination with ruxolitinib. The safety review committee (SRC) will determine the RP2D based on safety and efficacy data of the combination of TL-895 and ruxolitinib.	28 days
Primary	Phase 2 - Spleen Volume Reduction (SVR) at Week 24	The proportion of subjects achieving SVR of =35% at Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) scan.	24 Weeks
Secondary	Phase 1b - Spleen Volume Reduction (SVR) at Week 24	The proportion of subjects achieving =35% SVR at Week 24 by MRI or CT scan.	24 Weeks
Secondary	Phase 1b - TSS reduction at Week 24	The proportion of subjects achieving =50% reduction in TSS at Week 24 by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	24 Weeks
Secondary	Phase 2 - TSS reduction at Week 24	The proportion of subjects achieving =50% reduction in TSS at Week 24 by MFSAF v4.0.	24 Weeks
Secondary	DOR Spleen	Time from initial SVR of = 35% by MRI/CT until the first occurrence of disease progression or death	48 Months
Secondary	Progression Free Survival	Time from first dose to progression or death from any cause.	48 Month
Secondary	Overall Survival	Time from first dose to death from any cause	48 Months