Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
- Conditions
- MyelofibrosisPost-ET MyelofibrosisPost-PV MFPrimary Myelofibrosis
- Interventions
- Registration Number
- NCT05280509
- Lead Sponsor
- Telios Pharma, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
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.
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1b - Dose Level 1 TL-895 150 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. Phase 2 - Cohort 1 JAKi treatment-naïve MF 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. Phase 1b - Dose Level 3 TL-895 450 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. Phase 1b - Dose Level 1 Ruxolitinib 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. Phase 2 - Cohort 1 JAKi treatment-naïve MF TL-895 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. Phase 1b - Dose Level 2 TL-895 300 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. Phase 2 - Cohort 2 suboptimal response to Ruxolitinib TL-895 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. Phase 1b - Dose Level 2 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. Phase 1b - Dose Level 3 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. Phase 2 - Cohort 2 suboptimal response to Ruxolitinib 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.
- Primary Outcome Measures
Name Time Method Phase 2 - Spleen Volume Reduction (SVR) at Week 24 24 Weeks The proportion of subjects achieving SVR of ≥35% at Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib 28 days 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.
- Secondary Outcome Measures
Name Time Method Phase 2 - TSS reduction at Week 24 24 Weeks The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by MFSAF v4.0.
Progression Free Survival 48 Month Time from first dose to progression or death from any cause.
Phase 1b - TSS reduction at Week 24 24 Weeks The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
DOR Spleen 48 Months Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death
Overall Survival 48 Months Time from first dose to death from any cause
Phase 1b - Spleen Volume Reduction (SVR) at Week 24 24 Weeks The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan.
Trial Locations
- Locations (19)
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milano, Italy
Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
Hospital Quironsalud de Zaragoza
🇪🇸Zaragoza, Spain
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
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, United States
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, France
Marien Hospital Duesseldorf
🇩🇪Düsseldorf, Germany
Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
🇩🇪Halle, Germany
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
🇮🇹Bologna, Italy
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain