A Phase 1/2, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral Nuvisertib (TP-3654) in Patients With Intermediate or High-Risk Primary or Secondary Myelofibrosis
概览
- 阶段
- 1 期
- 干预措施
- Momelotinib
- 疾病 / 适应症
- Myelofibrosis
- 发起方
- Sumitomo Pharma America, Inc.
- 入组人数
- 240
- 试验地点
- 120
- 主要终点
- Determine the incidence of treatment emergent adverse events
- 状态
- 招募中
- 最后更新
- 18天前
概览
简要总结
This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary MF.
详细描述
Arm 1 will enroll patients who have been previously treated and failed on a JAK inhibitor or ineligible to receive treatment with a JAK inhibitor. Arm 2 will enroll patients who are on a stable dose of ruxolitinib, but who have either lost response or had a suboptimal or plateau in response. Arm 3 will enroll patients who have been previously treated with a JAK inhibitor (except momelotinib)
研究者
入排标准
入选标准
- •Patients must meet all of the following inclusion criteria to be eligible:
- •Nuvisertib (TP-3654) Monotherapy Arm:
- •Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF
- •Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be treated with JAK inhibitor
- •Fulfill the following clinical laboratory parameters:
- •Platelet count ≥ 25 x 10\^9 /L, without assistance of growth factors or platelet transfusions
- •ANC ≥ 1 x 10\^9/L without assistance of granulocyte growth factors
- •Peripheral blood blast count \< 5%
- •ECOG performance status ≤ 1
- •Life expectancy ≥ 6 months
排除标准
- •will be prohibited from participating in this study:
- •Nuvisertib (TP-3654) Monotherapy Arm:
- •Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day
- •Hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
- •Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or not recovered adequately from from surgery prior to first dose.
- •Splenic irradiation within 6 months prior to Screening or prior splenectomy.
- •Prior allogeneic stem cell transplant within the last 6 months.
- •Eligible for allogeneic bone marrow or stem cell transplantation.
- •Unresolved Grade ≥ 2 non-hematological toxicity related to prior treatment
- •History of symptomatic congestive heart failure, or myocardial infarction, or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) \< 45% by echocardiogram within 4 weeks prior to Cycle 1 Day
研究组 & 干预措施
Arm 3: nuvisertib (TP-3654) in combination with momelotinib
干预措施: Momelotinib
Arm 2: nuvisertib (TP-3654) added on to ruxolitinib
干预措施: Nusivertib
Arm 1: nuvisertib (TP-3654)
干预措施: Nusivertib
Arm 3: nuvisertib (TP-3654) in combination with momelotinib
干预措施: Nusivertib
Arm 2: nuvisertib (TP-3654) added on to ruxolitinib
干预措施: Ruxolitinib
结局指标
主要结局
Determine the incidence of treatment emergent adverse events
时间窗: From start of treatment to end of study
Number of participants with Treatment Emergent Adverse Events and Serious Adverse Events
Determine the incidence of dose-limiting toxicities (DLTs)
时间窗: 28 days
Number of participants with DLTs
Assess patients for any evidence of preliminary activity by determining the number of patients with ≥ 35% spleen volume reduction (SVR35)
时间窗: From start of treatment to end of study
Number of participants with ≥ 35% spleen volume reduction (SVR35)
次要结局
- Number of participants achieving objective response by IWG-MRT response criteria(From start of treatment to end of study)
- Number of participants who have ≥ 25% spleen volume reduction(Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks therafter during treatment.)
- Number of participants with ≥ 50% improvement in total symptom score (TSS50) at week 24(24 weeks)
- Determine the change in Patient Global Impression of Change (PGIC) at week 24 through end of study.(After 24 weeks of treatment to end of study)
- Determine the incidence of QT interval changes(25 hours)
- Establish the half-life (t½) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib(24 hours)
- Establish the Area under the plasma concentration versus time curve (AUC) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib(24 hours)
- Establish the Peak Plasma Concentration (Cmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib(24 hours)
- Establish the Time of Maximum concentration observed (tmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib(24 hours)