Clinical Trials /

Study of TL-895 in Subjects With Myelofibrosis

NCT04655118

Description:

This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis. Participants must be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study in Subjects With Myelofibrosis
  • Official Title: A Phase 2, Open-label, Multicenter Study of TL-895 in Subjects With Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis and Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: TL-895-201
  • NCT ID: NCT04655118

Conditions

  • Myelofibrosis

Interventions

DrugSynonymsArms
TL-895Arm 1 Expansion, Relapsed/Refractory Myelofibrosis

Purpose

This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis. Participants must be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment.

Trial Arms

NameTypeDescriptionInterventions
Arm 1a, Relapsed/Refractory MyelofibrosisExperimental150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
  • TL-895
Arm 1b, Relapsed/Refractory MyelofibrosisExperimental300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.
  • TL-895
Arm 2a, JAKi Intolerant MyelofibrosisExperimental150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
  • TL-895
Arm 2b, JAKi Intolerant MyelofibrosisExperimental300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.
  • TL-895
Arm 3a, JAKi Ineligible MyelofibrosisExperimental150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
  • TL-895
Arm 3b, JAKi Ineligible MyelofibrosisExperimental300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.
  • TL-895
Arm 1 Expansion, Relapsed/Refractory MyelofibrosisExperimentalTL-895 administered orally at RP2D and schedule
  • TL-895
Arm 2 Expansion, JAKi Intolerant MyelofibrosisExperimentalTL-895 administered orally at RP2D and schedule
  • TL-895
Arm 3 Expansion, JAKi Ineligble MyelofibrosisExperimentalTL-895 administered orally at RP2D and schedule
  • TL-895

Eligibility Criteria

        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

          -  Palpable spleen measuring ≥5 cm below the LLCM or spleen volume of ≥450 cm3 by MRI or
             CT scan assessment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

          -  Adequate hematologic, hepatic, and renal functions

        Exclusion Criteria:

          -  Prior treatment with any BCR-ABL, phosphoinositide 3-kinase (PI3K), mammalian target
             of rapamycin (mTOR), bromodomain and extraterminal domain (BET) or spleen tyrosine
             kinase (Syk) inhibitors

          -  Cohorts 1 and 2 - Prior treatment with JAKi within 21 days of the Screening MRI/CT
             scan. Subjects in Cohort 3 must not have received JAKi

          -  Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study
             treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary Objective, Part A: To determine the RP2D of TL-895 in each cohort.
Time Frame:9 months
Safety Issue:
Description:The safety review committee (SRC) will determine the RP2D for Cohorts 1, 2 and 3 based on safety and tolerability data obtained from each arm of that cohort.

Secondary Outcome Measures

Measure:Key Secondary Objective: Improvement in Total Symptom Score at Week 24.
Time Frame:Week 24
Safety Issue:
Description:The proportion of subjects achieving ≥50% reduction in Total Symptom Score at Week 24 by MFSAF v4.0.
Measure:Key Secondary Objective: To determine the duration of response (DOR).
Time Frame:44 months
Safety Issue:
Description:Time from initial response to progression.
Measure:Key Secondary Objective: To determine the progression-free survival (PFS).
Time Frame:44 months
Safety Issue:
Description:Time from the first dose to progression or death from any cause.
Measure:Key Secondary Objective: To determine the duration overall response (OS).
Time Frame:44 months
Safety Issue:
Description:Time from the first dose to death of any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Telios Pharma, Inc.

Last Updated

December 7, 2020