An Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of the BCL2 Inhibitor Sonrotoclax (BGB-11417) as Monotherapy and in Combination With Zanubrutinib (BGB-3111) in Patients With Waldenström Macroglobulinemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 114
- 试验地点
- 72
- 主要终点
- Cohort 1: Major Response Rate (MRR)
研究概览
简要总结
This study will evaluate the safety and efficacy of the BCL2 inhibitor sonrotoclax (BGB-11417) in participants with relapsed/refractory Waldenström's Macroglobulinemia (R/R WM) and in combination with zanubrutinib in adult participants with previously untreated WM.
详细描述
This study will test whether sonrotoclax (BGB-11417) can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) both when used alone in those who have not responded well to conventional treatments and when used in combination with zanubrutinib in those who have not yet received treatment. The main goals of the study are to determine how many participants no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment, and to determine what adverse events, or side effects, participants might experience.
BCL2 is a key protein involved in cell death, and abnormal levels of BCL2 are associated with many cancers. Blocking the action of BCL2 proteins is a promising approach with potential therapeutic benefits in participants with different types of cancers, including WM. This study will enroll approximately 105 participants. All participants will receive sonrotoclax orally as a tablet.
The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years.
Note: 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
- Non Randomized
- 干预模型
- Parallel
- 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
- •Clinical and definitive histologic diagnosis of WM.
- •Meeting ≥ 1 criterion for treatment according to consensus panel criteria from the 2nd International Workshop on Waldenström's Macroglobulinemia (IWWM).
- •For Cohorts 1-3, refractory or relapsed disease at study entry unless participants had intolerance to the most recent therapy. Refractory disease is defined as not attaining at least a major response, or progressing while on or within 6 months of completing therapy. Relapsed disease is defined as attaining at least a major response to therapy and meeting the criteria for disease progression beyond 6 months after completing therapy.
- •For Cohort 4, patients must not have received prior therapy for WM (except for plasmapheresis).
- •Adequate organ function.
排除标准
- •Central nervous system (CNS) involvement by WM.
- •Transformation to aggressive lymphoma, such as diffuse large B-cell lymphoma.
- •History of other malignancies ≤ 2 years before study entry.
- •Uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy that was completed ≤ 14 days before the first dose of the study drug.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 3
Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive sonrotoclax at a standard dose, given orally once daily.
干预措施: Sonrotoclax (Drug)
Cohort 1
Participants with R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor will receive sonrotoclax at a standard dose, given orally once daily.
干预措施: Sonrotoclax (Drug)
Cohort 2
Participants with R/R disease to anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor and were intolerant to BTK inhibitor will receive sonrotoclax at a standard dose, given orally once daily.
干预措施: Sonrotoclax (Drug)
Cohort 4
Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration.
干预措施: Sonrotoclax (Drug)
Cohort 4
Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration.
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Cohort 1: Major Response Rate (MRR)
时间窗: Up to approximately 4 years
MRR is defined as the percentage of participants achieving partial response (PR) or better, as assessed by the Independent Review Committee (IRC) per the 11th International Workshop on Waldenström Macroglobulinemia (IWWM-11) WM response criteria.
次要结局
- Cohorts 1, 2, and 3: Time to major response as assessed by the IRC(Up to approximately 5 years)
- All Cohorts: Time to major response as assessed by the investigator(Up to approximately 5 years)
- Cohorts 1, 2, and 3: Overall Survival (OS)(Up to approximately 5 years)
- Cohort 4: Time to next treatment(Up to approximately 5 years)
- Number of participants reporting adverse events(Up to approximately 5 years)
- Cohorts 2 and 3: MRR as assessed by the IRC(Up to approximately 5 years)
- All Cohorts: MRR as assessed by the Investigator(Up to approximately 5 years)
- Cohorts 1, 2, and 3: Duration of Major Response (DoMR) as assessed by the IRC(Up to approximately 5 years)
- All Cohorts: DoMR as assessed by the Investigator(Up to approximately 5 years)
- Cohorts 1, 2, and 3: Complete Response (CR) + Very Good Partial Response (VGPR) as assessed by the IRC(Up to approximately 5 years)
- All Cohorts: CR + VGPR as assessed by the Investigator(Up to approximately 5 years)
- Cohorts 1, 2, and 3: Overall Response Rate (ORR) as assessed by the IRC(Up to approximately 5 years)
- All cohorts: ORR as assessed by the investigator(Up to approximately 5 years)
- Cohorts 1, 2, and 3: Duration of Response (DOR) as assessed by the IRC(Up to approximately 5 years)
- All Cohorts: DOR as assessed by the investigator(Up to approximately 5 years)
- Cohorts 1, 2, and 3: Progression-Free Survival (PFS)(Up to approximately 5 years)
- All Cohorts: Change from Baseline in Health-Related Quality of Life (HRQoL): NFLymSI-18 Disease-related Symptoms-Physical and Treatment-Related Side Effects Subscales(Baseline and approximately months 7, 13, 19, and 25)