A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Combinations in Adult Patients With Myelofibrosis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Incidence of Dose limiting toxicities (DLT)
研究概览
简要总结
The purpose of this study is to investigate the safety, pharmacokinetics (PK) and preliminary efficacy of both the combination of MBG453 and NIS793 with or without decitabine or spartalizumab as well as single agent MBG453 and/or NIS793 single agent in myelofibrosis (MF) subjects post treatment with a Janus Kinase (JAK) inhibitor.
In this study, combination therapies with novel agents including immune therapy will focus on determining the promising combinations that provide acceptable safety and efficacy independent of JAK inhibitors. Immune therapy combinations, such as MBG453 in combination with NIS793, might offer the potential to target MF across genetic heterogeneity.
The primary objective of this study is to characterize the safety, tolerability and recomended dose for each treatment combination (MBG453 + NIS793, MBG453 + NIS793 + decitabine, and MBG453 + NIS793 + spartalizumab)
详细描述
The purpose of this study is to investigate the safety, pharmacokinetics (PK) and preliminary efficacy of both the combination of MBG453 and NIS793 with or without decitabine or spartalizumab as well as single agent MBG453 and/or NIS793 single agent in myelofibrosis (MF) subjects post treatment with a Janus Kinase (JAK) inhibitor.
In this study, combination therapies with novel agents including immune therapy will focus on determining the promising combinations that provide acceptable safety and efficacy independent of JAK inhibitors. Immune therapy combinations, such as MBG453 in combination with NIS793, might offer the potential to target MF across genetic heterogeneity.
The primary objective of this study is to characterize the safety, tolerability and recomended dose for each treatment combination (MBG453 + NIS793, MBG453 + NIS793 + decitabine, MBG453 + NIS793 + spartalizumab).
Secondary Objectives are: to evaluate the efficacy based on the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response criteria, to evaluate the effect of each combination treatment in delaying progression of MF and estimate time to progression free survival (PFS) event, and to characterize the PK profile of each treatment arm Study is designed as a Phase Ib, multi center, open label study with multiple treatment arms. The study is comprised of a dose evaluation/escalation part and a dose expansion part.
MBG453 in combination with NIS793 will be explored as the initial backbone. As the study progresses and based on emerging clinical data collected from this study, Novartis, in agreement with the study Investigators will decide whether or not:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
NIS793 + MBG453
treatment with NIS793 + MBG453
干预措施: MBG453 (Drug)
NIS793 + MBG453
treatment with NIS793 + MBG453
干预措施: NIS793 (Drug)
NIS793 + MBG453 + Spartalizumab
Treatment with NIS793 + MBG453 + Spartalizumab
干预措施: MBG453 (Drug)
NIS793 + MBG453 + Spartalizumab
Treatment with NIS793 + MBG453 + Spartalizumab
干预措施: NIS793 (Drug)
NIS793 + MBG453 + Spartalizumab
Treatment with NIS793 + MBG453 + Spartalizumab
干预措施: Spartalizumab (Drug)
NIS793 + MBG453 + Decitabine
treatment with NIS793 + MBG453 + Decitabine
干预措施: MBG453 (Drug)
NIS793 + MBG453 + Decitabine
treatment with NIS793 + MBG453 + Decitabine
干预措施: NIS793 (Drug)
NIS793 + MBG453 + Decitabine
treatment with NIS793 + MBG453 + Decitabine
干预措施: Decitabine (Drug)
NIS793
treatment with NIS793
干预措施: NIS793 (Drug)
MBG453
treatment with MBG453
干预措施: MBG453 (Drug)
结局指标
主要结局
Incidence of Dose limiting toxicities (DLT)
时间窗: 12 months
A dose-limiting toxicity (DLT) is defined as a clinically relevant adverse event or abnormal laboratory value where the relationship to study treatment cannot be ruled out, and which is unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the DLT monitoring period and meets any of the criteria included in Table 6-4 (Criteria for defining dose-limiting toxicities).
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
时间窗: 36 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and electrocardiograms (ECGs). A Serious adverse event (SAE) is defined as one of the following: * Is fatal or life-threatening * Results in persistent or significant disability/incapacity * Constitutes a congenital anomaly/birth defect * Is medically significant * Requires inpatient hospitalization or prolongation of existing hospitalization.
Dose interruptions
时间窗: 36 months
Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Dose reductions
时间窗: 36 months
Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Dose intensity
时间窗: 36 montths
Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity
次要结局
- Clinical benefit rate based on revised IWG-MRT (International Working Group Myelofibrosis Research & Treatment) criteria: complete response (CR), partial response (PR), stable disease, progressive disease (PD), Anemia response, Spleen response, relapse(36 months)
- Proportion of subjects achieving improvement of Anemia(36 months)
- Progression-free survial time (PFS)(36 months)
- Duration of response(36 months)
- Cmax (Maximum Concentration)(36 months)
- Tmax(36 months)