A Phase I/IIa, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-8263 in Adult Patients With Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 152
- 试验地点
- 2
- 主要终点
- Number of participants with dose limiting toxicities
研究概览
简要总结
This is a Phase 1/2a, first-in-human, open-label study of JAB-8263, this study has two parts: solid tumor dose escalation and expansion study and hematology tumor dose escalation and expansion study.
These two parts will determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and assess the DLT of JAB-8263 in treatment with patients with advanced solid tumors and hematology tumors separately. 30 subjects each will be enrolled.
详细描述
JAB-8263 is a small-molecule inhibitor of the highly conserved bromodomain pockets of the bromodomain and extraterminal (BET) proteins.
The objectives of this study are:
To determine the maximum-tolerated dose (MTD) and assess the dose-limiting toxicity (DLT) of JAB-8263 as a single agent to adult subjects with advanced malignant tumors. To assess the safety and tolerability of JAB-8263 To characterize the pharmacokinetic (PK) parameters and pharmacodynamics (PDc).To evaluate preliminary antitumor activity of JAB-8263
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
- •Subjects must meet all the following criteria in order to be included in the research study:
- •Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
- •Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed despite standard therapy(ies), or are intolerant to standard therapy(ies), or have a tumor for which no standard therapy(ies) exists.
- •Subjects with recurrent/refractory AML according to WHO 2016
- •Subjects with life expectancy ≥3 months.
- •Patients with solid tumor must have at least one measurable lesion as defined by RECIST v1.
- •Patients who have sufficient baseline organ function.
排除标准
- •History (≤3 years) of cancer that is histologically distinct from the cancer under study.
- •Known serious allergy to investigational drug or excipients
- •Active brain or spinal metastases
- •History of pericarditis or Grade ≥2 pericardial effusion
- •History of interstitial lung disease.
- •History of Grade ≥2 active infections within 2 weeks
- •Known human immunodeficiency virus (HIV) infection
- •Seropositive for hepatitis B virus (HBV)
- •Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable.
- •Any severe and/or uncontrolled medical conditions
- •History of myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident
- •Impaired cardiac function or clinically significant cardiac diseases
- •QTcF >470 msec at screening
- •History of medically significant thromboembolic events or bleeding diathesis
- •Unresolved Grade >1 toxicity
- •History of malignant biliary obstruction
- •Pregnant or breast-feeding
研究组 & 干预措施
JAB-8263 Part 2
Monotherapy, dose expansion
干预措施: JAB-8263 (Drug)
JAB-8263 Part1
Monotherapy, dose escalation
干预措施: JAB-8263 (Drug)
结局指标
主要结局
Number of participants with dose limiting toxicities
时间窗: Approximately 18 months
Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-8263
次要结局
- Number of participants with adverse events(Approximately 18 months)
- Area under the curve(Approximately 18 months)
- Cmax(Approximately 18 months)
- CR without minimal residual disease rate (CR MRD-)(Approximately 18 months)
- Duration of response ( DOR )(Approximately 18 months)
- T1/2(Approximately 18 months)
- Objective response rate ( ORR )(Approximately 18 months)
- Duration of response ( DCR )(Approximately 18 months)
- Event-free survival( EFS)(Approximately 18 months)
- Tmax(Approximately 18 months)
- Overall response rate(Approximately 18 months)