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

Telios Pharma

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Myelofibrosis; Primary Myelofibrosis; Post-ET Myelofibrosis; Post-PV MF

Treatments: Drug: Ruxolitinib; Drug: TL-895

Study type: Interventional

Funder types: Industry

Identifiers

NCT05280509

TL-895-209

Details and patient eligibility

About

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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

70 participants in 5 patient groups

Phase 1b - Dose Level 1

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: Ruxolitinib

Phase 1b - Dose Level 2

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: Ruxolitinib

Phase 1b - Dose Level 3

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: Ruxolitinib

Phase 2 - Cohort 1 JAKi treatment-naïve MF

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: Ruxolitinib

Phase 2 - Cohort 2 suboptimal response to Ruxolitinib

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: Ruxolitinib