A Multicenter, Open-Label, Phase 2 Study to Investigate the Efficacy and Safety of Sonrotoclax Combined With Zanubrutinib Compared With Zanubrutinib Monotherapy in Adult Patients With Previously Untreated Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 94
- 试验地点
- 57
- 主要终点
- Complete Response (CR)/ Complete Response with Incomplete Bone Marrow Recovery (CRi) Rate
研究概览
简要总结
The purpose of this study is to support the registration plan of sonrotoclax plus zanubrutinib treatment in participants with previously untreated chronic lymphocytic leukemia (CLL). This study is designed to assess the contribution of sonrotoclax to the efficacy outcome of the combination of zanubrutinib and sonrotoclax.
详细描述
This study will test how effective and safe Sonrotoclax plus Zanubrutinib treatment compared with Zanubrutinib alone in participants with previously untreated chronic lymphocytic leukemia (CLL).
The main goals of the study are to determine how many participants may 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, patients might experience.
Sonrotoclax is an experimental drug that works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood tumor cells to survive and grow. When Sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with CLL disease.
Zanubrutinib is a commercialized product that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B cells. Zanubrutinib has received approval in over 65 countries/regions worldwide for the treatment of adult participants with B cell malignancies, including CLL.
The study will enroll approximately 87 participants who will be randomly assigned by a computer program to receive one of the following treatments: sonrotoclax + zanubrutinib or zanubrutinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Previously untreated adult patient ≥ 18 years with a confirmed diagnosis of CLL.
- •CLL requiring treatment as per pre-defined criteria.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0,1, or
- •Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI).
- •Adequate marrow function.
- •Adequate liver function as indicated by aspartate aminotransferase (AST) alanine aminotransferase (ALT) and serum total bilirubin.
- •Adequate renal function.
- •Life expectancy > 6 months.
- •Signed informed consent and able to comply with the study protocol in the investigator's judgment.
- •Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 90 days after the last dose of study drug.
排除标准
- •Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
- •Known central nervous system involvement
- •Received previous systemic treatment for CLL
- •Clinically significant cardiovascular disease
- •Severe or debilitating pulmonary disease
- •History of prior malignancy
- •Active fungal, bacterial, and/or viral infection requiring systemic therapy
- •Positive human immunodeficiency virus (HIV) serology (HIVAb) status or serologic status reflecting active hepatitis B or C infection
- •Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment
- •History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- •History of stroke or intracranial hemorrhage ≤ 6 months before the first dose of study treatment
- •Unable to swallow capsules or tablets or diseases significantly affecting GI function
- •Hypersensitivity to zanubrutinib, sonrotoclax, or any of its excipients
- •Use of investigational agents within the last 4 weeks before screening
- •Pregnant and lactating females
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Arm A: Combination Therapy: Sonrotoclax + Zanubrutinib
Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.
干预措施: Zanubrutinib (Drug)
Arm B: Monotherapy: Zanubrutinib
Participants will receive zanubrutinib monotherapy daily until disease progression or unacceptable toxicity, whichever occurs first.
干预措施: Zanubrutinib (Drug)
Arm A: Combination Therapy: Sonrotoclax + Zanubrutinib
Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.
干预措施: Sonrotoclax (Drug)
结局指标
主要结局
Complete Response (CR)/ Complete Response with Incomplete Bone Marrow Recovery (CRi) Rate
时间窗: Month 16
Best CR/CRi rate per the Independent Review Committee (IRC) response assessment using the 2018 International Workshop on Chronic Lymphocytic Leukemia guidelines with modification for treatment-related lymphocytosis for participants with CLL
次要结局
- Undetectable Minimal Residual Disease at < 10^-4Sensitivity (uMRD4) Rate(Month 16)
- Time to Response (TTR) per IRC and Investigator Response Assessment(Up to 66 Months)
- Progression-free Survival (PFS) per Investigator Response Assessment(Up to 66 Months)
- Overall Survival (OS)(Up to 66 Months)
- CR/CRi Rate per Investigator Response Assessment(Month 16)
- Overall Response Rate (ORR) per IRC and Investigator Response Assessment(Up to 66 Months)
- Duration of Response (DOR) per Investigator Response Assessment(Up to 66 Months)
- Landmark Progression-free Survival Rate at 24 Months per Investigator Assessment(24 Months)
- Number of Participants with Adverse Events (AEs)(From first dose of study drug to 30 days after last dose; up to 66 months for Arm A and Arm B)