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

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1b - Dose Level 1 		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.
  • Drug: TL-895
    TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
  • Drug: Ruxolitinib
    Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
    Other names:
    • Jakafi
    • Jakavi
Experimental
Phase 1b - Dose Level 2 		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.
  • Drug: TL-895
    TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
  • Drug: Ruxolitinib
    Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
    Other names:
    • Jakafi
    • Jakavi
Experimental
Phase 1b - Dose Level 3 		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.
  • Drug: TL-895
    TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
  • Drug: Ruxolitinib
    Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
    Other names:
    • Jakafi
    • Jakavi
Experimental
Phase 2 - Cohort 1 JAKi treatment-naïve MF 		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.
  • Drug: TL-895
    TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
  • Drug: Ruxolitinib
    Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
    Other names:
    • Jakafi
    • Jakavi
Experimental
Phase 2 - Cohort 2 suboptimal response to 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 schedule will be the stable ruxolitinib dose schedule as the subject is currently taking prior to entry into the study.
  • Drug: TL-895
    TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
  • Drug: Ruxolitinib
    Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
    Other names:
    • Jakafi
    • Jakavi

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

More Details

Status
Recruiting
Sponsor
Telios Pharma, Inc.

Study Contact

John Mei
650-542-0136
jmei@teliospharma.com