Study of TL-895 in Subjects With Myelofibrosis or Indolent Systemic Mastocytosis

Telios Pharma

Status and phase: Enrolling; Phase 2

Conditions: Myelofibrosis; Indolent Systemic Mastocytosis

Treatments: Drug: Placebo; Drug: TL-895

Study type: Interventional

Funder types: Industry

Identifiers

NCT04655118

TL-895-201

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 (Cohorts 1-3) or Indolent Systemic Mastocytosis (Cohort 5). Participants must be diagnosed with Myelofibrosis and be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment, or be diagnosed with Indolent Systemic Mastocytosis.

Enrollment: 121 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Cohorts 1-3

Key Inclusion Criteria:

• Adults ≥18 years of age
• Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• Adequate hematologic, hepatic, and renal functions
• MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 for each of the 2 symptoms per MFSAF v4.0
• Cohort 3 only: Ineligibility for JAKi treatment with a platelet count of ≥ 25 and < 50 x 10^9/L

Key Exclusion Criteria:

• Prior treatment with any BTK or BMX inhibitors
• Prior treatment with JAKi within 28 days prior to study treatment
• Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment

Cohort 5

Key Inclusion Criteria:

• Adults ≥18 years of age
• Confirmed diagnosis of ISM as defined by WHO diagnostic criteria based on review of bone marrow biopsy pathology report results
• Subject must have moderate-to-severe symptoms

Key Exclusion Criteria:

• Prior treatment with any BTK or BMX inhibitors
• Prior treatment with Avapritinib, bezuclastinib, or BLU-263/elenestinib
• Diagnosis with another myeloproliferative disorder

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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121 participants in 13 patient groups, including a placebo group

Cohort 1a, Relapsed/Refractory Myelofibrosis

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.

Treatment:

Drug: TL-895

Cohort 1b, Relapsed/Refractory Myelofibrosis

Experimental group

Description:

300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Treatment:

Drug: TL-895

Cohort 1c, Relapsed/Refractory Myelofibrosis

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.

Treatment:

Drug: TL-895

Cohort 1d, Relapsed/Refractory Myelofibrosis

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.

Treatment:

Drug: TL-895

Cohort 2a, JAKi Intolerant Myelofibrosis

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.

Treatment:

Drug: TL-895

Cohort 2b, JAKi Intolerant Myelofibrosis

Experimental group

Description:

300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Treatment:

Drug: TL-895

Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L

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.

Treatment:

Drug: TL-895

Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L

Experimental group

Description:

300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Treatment:

Drug: TL-895

Cohort 5a, Indolent Systemic Mastocytosis

Experimental group

Description:

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with best supportive care (BSC).

Treatment:

Drug: TL-895

Cohort 5b, Indolent Systemic Mastocytosis

Experimental group

Description:

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Treatment:

Drug: TL-895

Cohort 5c, Indolent Systemic Mastocytosis

Experimental group

Description:

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Treatment:

Drug: TL-895

Cohort 5d, Indolent Systemic Mastocytosis

Experimental group

Description:

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Treatment:

Drug: TL-895

Cohort 5e, Indolent Systemic Mastocytosis

Placebo Comparator group

Description:

Placebo to match TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Treatment:

Drug: Placebo