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

Primary Purpose

Myelofibrosis, Primary Myelofibrosis, Post-PV MF

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TL-895
Ruxolitinib
Sponsored by
Telios Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • Gabrail Cancer CenterRecruiting
  • University of Cincinnati (UC)Recruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • CHU AngersRecruiting
  • AP-HM - Hôpital de la TimoneRecruiting
  • CHU de Nice - Hopital L'Archet IIRecruiting
  • Hôpital Saint Louis - AP-HPRecruiting
  • Centre Hospitalier Lyon SudRecruiting
  • Marien Hospital DuesseldorfRecruiting
  • Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum HallRecruiting
  • IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'OrsolaRecruiting
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di MilanoRecruiting
  • Azienda Ospedaliera di Perugia-Ospedale S. Maria della MisericordiaRecruiting
  • Pratia Onkologia KatowiceRecruiting
  • Hospital Universitari Arnau de VilanovaRecruiting
  • Hospital Universitario Ramon y CajalRecruiting
  • Hospital Universitario Virgen de la VictoriaRecruiting
  • Hospital Quironsalud de ZaragozaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1b - Dose Level 1

Phase 1b - Dose Level 2

Phase 1b - Dose Level 3

Phase 2 - Cohort 1 JAKi treatment-naïve MF

Phase 2 - Cohort 2 suboptimal response to Ruxolitinib

Arm Description

150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.

300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.

450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.

The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose of ruxolitinib will be based on the subject's baseline platelet count.

The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose schedule will be the stable ruxolitinib dose schedule as the subject is currently taking prior to entry into the study.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Phase 1b - Spleen Volume Reduction (SVR) at Week 24
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan.
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.
Phase 2 - TSS reduction at Week 24
The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by MFSAF v4.0.
DOR Spleen
Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death
Progression Free Survival
Time from first dose to progression or death from any cause.
Overall Survival
Time from first dose to death from any cause

Full Information

First Posted
March 5, 2022
Last Updated
February 16, 2023
Sponsor
Telios Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05280509
Brief Title
Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 9, 2022 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
April 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Telios Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis, Primary Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis
Keywords
Myelofibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b - Dose Level 1
Arm Type
Experimental
Arm Description
150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.
Arm Title
Phase 1b - Dose Level 2
Arm Type
Experimental
Arm Description
300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.
Arm Title
Phase 1b - Dose Level 3
Arm Type
Experimental
Arm Description
450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.
Arm Title
Phase 2 - Cohort 1 JAKi treatment-naïve MF
Arm Type
Experimental
Arm Description
The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose of ruxolitinib will be based on the subject's baseline platelet count.
Arm Title
Phase 2 - Cohort 2 suboptimal response to Ruxolitinib
Arm Type
Experimental
Arm Description
The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose schedule will be the stable ruxolitinib dose schedule as the subject is currently taking prior to entry into the study.
Intervention Type
Drug
Intervention Name(s)
TL-895
Intervention Description
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi, Jakavi
Intervention Description
Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
Primary Outcome Measure Information:
Title
Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib
Description
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.
Time Frame
28 days
Title
Phase 2 - Spleen Volume Reduction (SVR) at Week 24
Description
The proportion of subjects achieving SVR of ≥35% at Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
Time Frame
24 Weeks
Secondary Outcome Measure Information:
Title
Phase 1b - Spleen Volume Reduction (SVR) at Week 24
Description
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan.
Time Frame
24 Weeks
Title
Phase 1b - TSS reduction at Week 24
Description
The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Time Frame
24 Weeks
Title
Phase 2 - TSS reduction at Week 24
Description
The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by MFSAF v4.0.
Time Frame
24 Weeks
Title
DOR Spleen
Description
Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death
Time Frame
48 Months
Title
Progression Free Survival
Description
Time from first dose to progression or death from any cause.
Time Frame
48 Month
Title
Overall Survival
Description
Time from first dose to death from any cause
Time Frame
48 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Mei
Phone
650-542-0136
Email
jmei@teliospharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Nikki Stuart
Email
nzona@teliospharma.com
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Cincinnati (UC)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
CHU Angers
City
Angers
ZIP/Postal Code
49100
Country
France
Individual Site Status
Recruiting
Facility Name
AP-HM - Hôpital de la Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Nice - Hopital L'Archet II
City
Nice
ZIP/Postal Code
06200
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Saint Louis - AP-HP
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Name
Marien Hospital Duesseldorf
City
Düsseldorf
ZIP/Postal Code
40479
Country
Germany
Individual Site Status
Recruiting
Facility Name
Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
City
Halle
ZIP/Postal Code
40479
Country
Germany
Individual Site Status
Recruiting
Facility Name
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
City
Milano
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Name
Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
City
Perugia
ZIP/Postal Code
06129
Country
Italy
Individual Site Status
Recruiting
Facility Name
Pratia Onkologia Katowice
City
Katowice
ZIP/Postal Code
40-519
Country
Poland
Individual Site Status
Recruiting
Facility Name
Hospital Universitari Arnau de Vilanova
City
Lleida
ZIP/Postal Code
25198
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen de la Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Quironsalud de Zaragoza
City
Zaragoza
ZIP/Postal Code
50006
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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