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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Myelofibrosis; Myelofibrosis; Post-PV MF; Post-ET Myelofibrosis
• Intervention / Treatment: Drug: TL-895; Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: John Mei; Phone Number: 650-542-0136; Email: jmei@teliospharma.com
• Study Contact Backup: Name: Nikki Stuart; Email: nzona@teliospharma.com

Study Locations

• France
  • Angers, France, 49100
    • Recruiting
    • Chu Angers
  • Marseille, France, 13005
    • Recruiting
    • AP-HM - Hôpital de la Timone
  • Nice, France, 06200
    • Recruiting
    • CHU de Nice - Hôpital l'Archet II
  • Paris, France, 75010
    • Recruiting
    • Hôpital Saint Louis - AP-HP
  • Pierre-Bénite, France, 69495
    • Recruiting
    • Centre Hospitalier Lyon Sud
• Germany
  • Düsseldorf, Germany, 40479
    • Recruiting
    • Marien Hospital Duesseldorf
  • Halle, Germany, 40479
    • Recruiting
    • Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
  • Milano, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Perugia, Italy, 06129
    • Recruiting
    • Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
• Poland
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Onkologia Katowice
• Spain
  • Lleida, Spain, 25198
    • Recruiting
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
  • Zaragoza, Spain, 50006
    • Recruiting
    • Hospital Quironsalud de Zaragoza
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati (UC)
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
DOR Spleen	Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death	48 Months
Progression Free Survival	Time from first dose to progression or death from any cause.	48 Month
Overall Survival	Time from first dose to death from any cause	48 Months

Collaborators and Investigators

• Sponsor: Telios Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Anticipated): October 1, 2025
• Study Completion (Anticipated): April 1, 2027

Study Registration Dates

• First Submitted: March 5, 2022
• First Submitted That Met QC Criteria: March 5, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Myelofibrosis
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: TL-895-209

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No