NCT07008118招募中1 期
A Phase 1, Open-Label, Multicenter Study of INCA035784 in Participants With Myeloproliferative Neoplasms
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 35
- 主要终点
- Number of participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study is being conducted to evaluate the safety and tolerability of INCA035784 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 or older at the time of signing the ICF
- •ECOG performance status of 0 to 1 for the dose escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b)
- •Documented CALR exon-9 mutation
- •Confirmed diagnosis of MPN according to the 2022 ICC criteria:
- •DIPSS+ intermediate-2/high-risk MF with prior JAKi, <20% blasts, and measurable spleen
- •High-risk ET with platelets >450×10⁹/L
- •Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET (unless only a single standard-of-care option is approved in the participating country)
- •No prior stem cell transplant and none planned within 6 months
- •Minimum Laboratory Requirements:
- •Platelet count ≥50 × 10⁹/L
- •Absolute neutrophil count ≥1 × 10⁹/L
- •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN), unless receiving vitamin K antagonists
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 × ULN
- •Total bilirubin <2 × ULN
- •Estimated creatinine clearance >45 or >30 mL/min (depending on study part)
排除标准
- •Major bleeding or thrombosis (e.g., stroke, DVT, PE) within the past 3 months
- •Active or high-risk HBV, HCV, or HIV infection, or other chronic active infections requiring systemic treatment
- •Active invasive cancer within the past 2 years, except certain early-stage or low-risk cancers (e.g., resected skin, cervical, thyroid, or prostate cancer)
- •Pregnant or unwilling to avoid pregnancy or fathering a child during the study and for a defined period after the last dose.
- •Other protocol-defined Inclusion/Exclusion Criteria may apply.
研究组 & 干预措施
Part 1a: Dose escalation
Experimental
INCA035784 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myeloproliferative neoplasm (MPN) will enroll in this group.
干预措施: INCA035784 (Drug)
Part 1b: Dose expansion
Experimental
INCA035784 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with myeloproliferative neoplasm (MPN) will enroll in this group.
干预措施: INCA035784 (Drug)
结局指标
主要结局
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.
Number of participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 2 years and 90 days
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after the last dose of study drug.
Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay
时间窗: Up to approximately 2 years and 90 days
Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay.
次要结局
- Number of participants with TEAEs leading to dose modification or discontinuation(Up to approximately 2 years and 90 days)
- Participants with MF: Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria for myelofibrosis (MF)(Up to approximately 2 years and 90 days)
- Participants with essential thrombocythemia (ET): Response using the revised IWG-MRT and ELN response criteria for ET(Up to approximately 2 years and 90 days)
- Participants with myelodysplastic syndrome (MDS)/MPN: Response using the revised IWG-MRT response criteria for MDS/MPN(Up to approximately 2 years and 90 days)
- Participants with symptomatic anemia: Anemia response(Up to approximately 2 years and 90 days)
- Participants with spleen volume (SV) ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 35% (SVR35)(Week 12 and Week 24)
- Participants with SV ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 25% (SVR25)(Week 12 and Week 24)
- Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)(Week 12 and Week 24)
- Mean change from baseline in TSS(Week 12 and Week 24)
- Pharmacokinetics Parameter (PK): Cmax of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: Tmax of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: Cmin of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: AUC(0-t) of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: AUC 0-∞ of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: CL of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: Vz of INCA035784(Up to approximately 2 years and 90 days)
- Pharmacokinetics Parameter: t1/2 of INCA035784(Up to approximately 2 years and 90 days)
研究者
研究点 (35)
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