A Phase 1, Open-Label, Multicenter Study of INCA036978 in Participants With Myeloproliferative Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 218
- 试验地点
- 54
- 主要终点
- Number of participants with Dose Limiting Toxicities (DLT)s in Part 1
研究概览
简要总结
This study will be conducted to determine the safety, tolerability, dose-limiting toxicity (DLT)s, and maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)s of INCA036978 administered as monotherapy and in combination with a standard disease-directed therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Life expectancy > 6 months.
- •Willingness to undergo a pretreatment and limited on-study BM biopsies and aspirates (as appropriate to disease).
- •Participants with MF, PV and ET as defined in the protocol.
排除标准
- •Presence of any hematological malignancy other than MF, PV, or ET.
- •Malignancy within the last 3 years prior to enrollment.
- •Acute or chronic HBV, Active HCV or known HIV or tuberculosis infection.
- •Clinically significant or uncontrolled cardiac disease.
- •Has undergone any prior allogeneic stem-cell transplantation or such transplantation is planned in the next 6 months.
- •Laboratory values outside the Protocol-defined ranges.
- •Prior history of major bleeding or thrombosis within the last 3 months prior to study enrollment.
- •Presence of chronic or current active infectious disease requiring systemic treatment.
- •Treatment with an MPN-directed therapy (approved or investigational) within the per protocol threshold before the administration of study drug.
- •Prior radiation therapy within 28 days before the first dose of study treatment.
- •Other protocol-defined Inclusion/Exclusion Criteria may apply.
研究组 & 干预措施
Part 1b: Dose Escalation
INCA036978 will be administered at a protocol defined starting regimen in combination with a standard disease-directed therapy to identify the MTD and/or RDE(s).
干预措施: INCA036978 (Drug)
Part 1b: Dose Escalation
INCA036978 will be administered at a protocol defined starting regimen in combination with a standard disease-directed therapy to identify the MTD and/or RDE(s).
干预措施: Standard disease-directed therapy (Drug)
Part 2a: Dose Expansion
INCA036978 will be administered as monotherapy at the RDE(s) identified during Part 1
干预措施: INCA036978 (Drug)
Part 2b: Dose Expansion
INCA036978 will be administered in combination with a standard disease-directed therapy at the RDE(s) identified during Part 1.
干预措施: INCA036978 (Drug)
Part 2b: Dose Expansion
INCA036978 will be administered in combination with a standard disease-directed therapy at the RDE(s) identified during Part 1.
干预措施: Standard disease-directed therapy (Drug)
Part 1a: Dose Escalation
INCA036978 will be administered at a protocol defined starting regimen as monotherapy to identify the MTD and/or RDE(s).
干预措施: INCA036978 (Drug)
结局指标
主要结局
Number of participants with Dose Limiting Toxicities (DLT)s in Part 1
时间窗: Up to 28 days
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Number of participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 2 years
Defined as adverse events AE (either reported for the first time or the worsening of a pre-existing event) occurring after the first dose of study drug and up to 60 days after last dose of study drug or until the start of a new disease-directed therapy, whichever occurs first.
Number of participants with TEAEs leading to dose modification or discontinuation
时间窗: Up to approximately 2 years
Number of participants with TEAEs leading to study drug modifications (interruptions, dose reduction) or discontinuation.
次要结局
- Pharmacokinetics Parameter: Cmin,ss of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: AUC 0-∞ of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: Cmax of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: Tmax of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: Cmax,ss of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: AUC(0-t) of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: CL/F of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: Vz/F of INCA036978(Up to approximately 2 years)
- Pharmacokinetics Parameter: t1/2 of INCA036978(Up to approximately 2 years)
- For participants with myelofibrosis (MF): Percentage of participants achieving spleen volume reduction as defined in the protocol(Week 12 and Week 24)
- For participants with MF and anemia: Anemia Response as defined in the protocol(Up to approximately 2 years)
- For participants with polycythemia vera (PV): Peripheral blood count remission as defined by the protocol.(Up to approximately 2 years)
- For participants with essential thrombocythemia (ET): Peripheral blood count remission as defined by the protocol.(Up to approximately 2 years)