A Multicenter, Open-Label Phase I/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics/ Pharmacodynamics and Efficacy of BR1733 Monotherapy in Subjects With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 191
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT, Phase Ⅰ only)
研究概览
简要总结
This study is a Phase I/IIa, multi-center, open-label study of BR1733 with a dose escalation part followed by a dose expansion part in adult subjects with advanced cancers.
This treatment to characterize the safety, tolerability, PK, PD and preliminary antitumor activity.
The study treatment will be administered until the subject experiences unacceptable toxicity, progressive disease, and/or has treatment discontinued at the discretion of the Investigator or the subject, or due to withdrawal of consent.
详细描述
This is a multi-center, nonrandomized, open-label study to evaluate the safety, tolerability, pharmacokinetics/ pharmacodynamics, and efficacy of BR1733 in patients with advance cancer, such as recurrent/refractory follicular lymphoma, peripheral T cell lymphoma(PTCL), diffuse large B cell lymphoma(DLBCL) and advance solid tumors.
Phase Ⅰ (Dose Escalation Phase): According to the incidence of DLT in BR1733 tablets in the treatment of advanced cancers, MTD and the Phase 2 clinical trial dose (RP2D) combining PK, PD, efficacy and safety data were determined.
Phase IIa (Dose expansion stage): Evaluate the efficacy and safety of BR1733 monotherapy (Cohorts 1-5) in five separate cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Sign informed consent voluntarily.
- •Subjects with PTCL, DLBCL or advance solid tumors diagnosed by histology or cytology，whose disease progressed after standard treatment or have no standard treatment.
- •Expected survival period ≥ 3 months.
- •Adequate organ function reserve at baseline.
排除标准
- •Subjects with symptomatic central nervous system (CNS) metastases or carcinomatous meningitis;
- •Subjects with a history of other primary malignancies within 5 years (except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumor), subjects with other primary tumors who had no evidence of disease for 5 years or more and did not require treatment could participate in the study;
- •Subjects with any severe uncontrolled disease such as liver disease such as cirrhosis, decompensated liver disease, kidney failure needs for hemodialysis or peritoneal dialysis, etc.
- •Subjects with HIV disease or a positive HIV test; or active hepatitis.
- •Subjects with organ transplantation (apart from keratoplasty) or allogeneic hematopoietic stem cell transplantation.
- •Subjects with impaired or clinically significant cardiac cerebrovascular disease.
- •Subjects known to be allergic to experimental drugs or similar compounds.
- •Subjects known with psychotropic substance abuse, alcohol or drug abuse, or mental disorders.
- •Any previous treatment with other EED inhibitors (e.g., MAK683, FTX-6058, etc.).
- •Females who are pregnant or breastfeeding.
研究组 & 干预措施
BR1733
25-1200 mg QD or BID
干预措施: BR1733 (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT, Phase Ⅰ only)
时间窗: 28 day cycle of therapy
To assess adverse events as dose limiting toxicities as defined by the protocol.
Objective Response Rate (ORR, Phase Ⅱa)
时间窗: 24 months
The proportion of patients with a best response of at least partial remission (including partial remission and complete remission) using disease appropriate standardized response criteria.
次要结局
- Area under curve (AUC) of BR1733 monotherapy(28 day cycle of therapy)
- Area under curve, steady state (AUCss) of BR1733 monotherapy(28 day cycle of therapy)
- Halflife (T1/2) of BR1733 monotherapy(28 day cycle of therapy)
- Maximum plasma concentration, steady state (Cmax,ss) of BR1733 monotherapy(28 day cycle of therapy)
- Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability(Up to 2 years)
- Maximum plasma concentration (Cmax) of BR1733 monotherapy(28 day cycle of therapy)
- Progression-free survival (PFS)(Up to 2 years)
- Clearance/ bioavailability (CL/F) of BR1733 monotherapy(28 day cycle of therapy)
- Duration of Response (DoR)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)