A Phase 1, Open-Label, Multicenter Study of INCB160058 in Participants With Myeloproliferative Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 37
- 试验地点
- 50
- 主要终点
- Number of participants with TEAEs leading to dose modification or discontinuation
研究概览
简要总结
This study is being conducted to assess the Safety, Tolerability, and Pharmacokinetics of INCB160058 in Participants With Myeloproliferative Neoplasms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Age ≥ 18 years
- •Intermediate-1 or higher risk PMF, post-PV MF, or post-ET MF with evidence of minimum burden of disease based on splenomegaly, and for the monotherapy cohort, participants must have been previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment.
- •For the MF SubOpt R cohort: Therapeutic regimen prior to enrollment as defined in the protocol and unlikely to benefit from further monotherapy in the opinion of the investigator.
- •PV: Confirmed diagnosis of PV and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment.
- •ET: Confirmed diagnosis of high-risk ET as defined in the protocol and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment.
- •Life expectancy > 6 months.
- •Willingness to undergo a pretreatment and regular on-study bone marrow biopsies and aspirations (as appropriate to disease).
- •Existing documentation of JAK2V617F mutation from a qualified local laboratory.
排除标准
- •Presence of a hematological malignancy requiring treatment, other than PMF, post-PV MF, post-ET MF, PV, or ET.
- •Prior history of major bleeding or thrombosis within the 3 months prior to study enrollment.
- •Participants with abnormal hematologic, hepatic, or renal function based on laboratory evaluation.
- •Has undergone prior allogenic or autologous stem-cell transplantation or allogenic stem-cell transplantation is planned
- •Active invasive malignancy.
- •Significant concurrent, uncontrolled medical condition.
- •Acute or chronic HBV, active HCV or known HIV.
- •Any prior MPN-directed therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
- •Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at any time within 4 weeks before the first dose of study treatment.
- •Other protocol-defined Inclusion/Exclusion Criteria may apply.
研究组 & 干预措施
Part 1 Dose Escalation - with MF SubOpt R
INCB160058 will be administered at a protocol defined starting regimen and will allow for the evaluation of INCB160058 in combination with a standard disease-directed therapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF), suboptimal response to a standard disease-directed therapy (SubOpt R) will enroll in this group.
干预措施: Standard disease-directed therapy (Drug)
Part 1 Dose Escalation - with MF, PV or ET
INCB160058 will be administered at a protocol defined starting regimen to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF), polycythemia vera (PV) or essential thrombocythemia (ET) will enroll in this group.
干预措施: INCB160058 (Drug)
Part 2 Dose Expansion - with MF SubOpt R
INCB160058 will be administered as an add-on therapy in combination with a standard disease-directed therapy at the RDE(s) identified during Part 1. Participants with myelofibrosis (MF), suboptimal response to a standard disease-directed therapy (SubOpt R) will enroll in this group.
干预措施: Standard disease-directed therapy (Drug)
Part 2 Dose Expansion - with MF SubOpt R
INCB160058 will be administered as an add-on therapy in combination with a standard disease-directed therapy at the RDE(s) identified during Part 1. Participants with myelofibrosis (MF), suboptimal response to a standard disease-directed therapy (SubOpt R) will enroll in this group.
干预措施: INCB160058 (Drug)
Part 2 Dose Expansion - with MF, PV or ET
INCB160058 will be administered at the RDE(s) identified during Part 1. Participants with MF, PV or ET will enroll in this group.
干预措施: INCB160058 (Drug)
Part 1 Dose Escalation - with MF SubOpt R
INCB160058 will be administered at a protocol defined starting regimen and will allow for the evaluation of INCB160058 in combination with a standard disease-directed therapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF), suboptimal response to a standard disease-directed therapy (SubOpt R) will enroll in this group.
干预措施: INCB160058 (Drug)
结局指标
主要结局
Number of participants with TEAEs leading to dose modification or discontinuation
时间窗: Up to 2 years and 30 days
Number of participants with TEAEs leading to dose modification or discontinuation.
Number of participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 2 years and 30 days
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
Number of participants with Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
次要结局
- For all participants: Symptom improvement in TSS at Weeks 12 and 24 relative to baseline as measured by the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) TSS.(Week 12 and Week 24)
- For participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF(Week 12 and 24 and then every 24 weeks up to 2 years)
- For participants with MF: Percentage of participants achieving spleen volume reduction as defined in the protocol(Week 12 and Week 24)
- For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV(Week 12 and 24 and then every 24 weeks up to 2 years)
- For participants with ET: Response using revised IWG-MRT and ELN response criteria for ET(Week 12 and 24 and then every 24 weeks up to 2 years)
- For all participants: Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)(Week 24)
- INCB160058 and a standard disease-directed therapy pharmacokinetic (PK) in Plasma(Up to Day 57)
- For participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF(Week 12 and 24 and then every 24 weeks up to 2 years)
- For participants with MF: Percentage of participants achieving spleen volume reduction as defined in the protocol(Week 12 and Week 24)
- For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV(Week 12 and 24 and then every 24 weeks up to 2 years)
- For participants with ET: Response using revised IWG-MRT and ELN response criteria for ET(Week 12 and 24 and then every 24 weeks up to 2 years)
- For all participants: Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)(Week 24)
- For all participants: Symptom improvement in TSS at Weeks 12 and 24 relative to baseline as measured by the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) TSS.(Week 12 and Week 24)