Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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:
|
| 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:
|
| 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:
|
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
Secondary Outcome Measures
- 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.
- 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.
- 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.
- DOR Spleen [48 Months]
Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death
- Progression Free Survival [48 Month]
Time from first dose to progression or death from any cause.
- Overall Survival [48 Months]
Time from first dose to death from any cause
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gabrail Cancer Center | Canton | Ohio | United States | 44718 |
Sponsors and Collaborators
- Telios Pharma, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TL-895-209