A Phase 2 Multicenter Study of TL-895 in Subjects With Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis, Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis, or Indolent Systemic Mastocytosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 121
- 试验地点
- 52
- 主要终点
- Cohorts 1-3: Determine the RP2D of TL-895
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Cohort 1a, Relapsed/Refractory Myelofibrosis
150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 1b, Relapsed/Refractory Myelofibrosis
300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 1c, Relapsed/Refractory Myelofibrosis
300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 1d, Relapsed/Refractory Myelofibrosis
450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 2a, JAKi Intolerant Myelofibrosis
150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 2b, JAKi Intolerant Myelofibrosis
300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L
150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L
300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.
干预措施: TL-895 (Drug)
Cohort 5a, Indolent Systemic Mastocytosis
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).
干预措施: TL-895 (Drug)
Cohort 5b, Indolent Systemic Mastocytosis
TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.
干预措施: TL-895 (Drug)
Cohort 5c, Indolent Systemic Mastocytosis
TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.
干预措施: TL-895 (Drug)
Cohort 5d, Indolent Systemic Mastocytosis
TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.
干预措施: TL-895 (Drug)
Cohort 5e, Indolent Systemic Mastocytosis
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Cohorts 1-3: Determine the RP2D of TL-895
时间窗: 9 months
The RP2D for Cohorts 1, 2 and 3 will be reported
Cohort 5: Determine the RP2D of TL-895
时间窗: Week 24
The RP2D for Cohort 5 will be reported
次要结局
- Cohort 5: Changes in patient reported symptoms(Week 12)
- Cohorts 1-3: Spleen volume reduction (SVR) rate(Week 24)