A Phase 1/1b Open-Label Dose-Escalation and Dose-Optimization Study of Bcl-2 Inhibitor BGB-21447 in Patients With Mature B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 51
- 试验地点
- 28
- 主要终点
- Part 1: Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
This study is testing the safety and tolerability of BGB-21447 monotherapy in participants with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study aims to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), recommended Phase 2 dose (RP2D), and pharmacokinetic profile of the drug. Additionally, preliminary antitumor activity will be characterized. The study is divided into 2 main parts: Part 1 "Monotherapy Dose Finding" and Part 2 "Monotherapy Dose Optimization."
详细描述
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
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
- •Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following:
- •Cohort A1 and Cohort A2:
- •R/R DLBCL (for Cohort A1 and Cohort A2.1)
- •High-grade B-cell lymphomas with translocations of MYC and Bcl-2 and/or Bcl-6 are not allowed in Cohort A1 but may be allowed in Cohort A2.1
- •R/R FL (for Cohort A1 and Cohort A2.2)
- •R/R MZL (for Cohort A1 and Cohort A2.2)
- •Transformed B-cell NHL (for Cohort A1 only)
- •Richter's transformation to DLBCL (for Cohort A1 only)
- •Measurable disease by computed tomography/magnetic resonance imaging.
排除标准
- •Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer or lentigo maligna melanoma that has been curatively resected
- •Known central nervous system involvement by lymphoma/leukemia
- •Prior autologous stem cell transplant < 3 months before the first dose of study drug. Or prior chimeric antigen receptor T-cell (CAR-T) therapy < 3 months before the first dose of study drug
- •Prior allogeneic stem cell transplant.
- •Major surgery < 4 weeks before the first dose of study treatment
- •NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 2 (Cohort A2.1): BGB-21447 Monotherapy Dose Optimization in R/R DLBCL
Participants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.
干预措施: BGB-21447 (Drug)
Part 1 (Cohort B): Dose escalation in R/R CLL/SLL participants with low tumor burden
Participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive BGB-21447 once a day.
干预措施: BGB-21447 (Drug)
Part 1 (Cohort A1): Dose escalation in patients with B-cell non-Hodgkin lymphoma (NHL)
Participants with R/R B-cell NHL (including diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], marginal zone lymphoma [MZL], transformed B-cell NHL (B-NHL), and Richter's transformation to DLBCL) will receive BGB-21447 once a day.
干预措施: BGB-21447 (Drug)
Part 2 (Cohort A2.2): BGB-21447 Monotherapy Dose Optimization in R/R FL or R/R MZL
Participants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.
干预措施: BGB-21447 (Drug)
结局指标
主要结局
Part 1: Number of participants with dose limiting toxicities (DLTs)
时间窗: Up to approximately 1 month
Number of participants with dose limiting toxicities, as defined in the study protocol.
Number of participants with adverse events (AEs)
时间窗: From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed and graded based upon the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
Number of participants with Tumor Lysis Syndrome (TLS)
时间窗: From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months
TLS will be determined via laboratory values and assessed by the investigator. In laboratory tumor lysis syndrome, 2 or more metabolic abnormalities must be present during the 24-hour period within 3 days before the start of study drug treatment or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.
次要结局
- Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Area under the curve from time 0 to the last sampling time point within the dose interval (AUC0-t) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Area under the curve from time 0 extrapolated to infinity time (AUCinf) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Time to reach maximum observed plasma concentration (Tmax) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Apparent terminal elimination half-life (t1/2) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Apparent oral clearance (CL/F) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Apparent volume of distribution (Vz/F) After a Single Dose of BGB-21447(Up to approximately 8 weeks)
- Steady state maximum observed plasma concentration (Cmax,ss) of BGB-21447(Up to approximately 8 weeks)
- Steady state pre-dose trough concentration (Ctrough,ss) of BGB-21447(Up to approximately 8 weeks)
- Steady state area under the curve from time 0 to the quantifiable concentration (AUClast,ss) of BGB-21447(Up to approximately 8 weeks)
- Steady state time to reach maximum observed plasma concentration (Tmax,ss) of BGB-21447(Up to approximately 8 weeks)
- Overall response rate (ORR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Time to response (TTR)(Up to approximately 24 months)
- Part 2: Progression-free survival (PFS)(Up to approximately 24 months)