A Single-arm, Phase 2, Open-label, Multicenter Study to Evaluate NX-5948 in Adults With Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Previously Exposed to a Bruton's Tyrosine Kinase Inhibitor (BTKi) and a B-cell Lymphoma-2 Inhibitor (BCL-2i)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 40
- 主要终点
- Objective response rate without partial response with lymphocytosis (PR-L) as determined by an Independent Review Committee (IRC)
研究概览
简要总结
This is a study for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with a BTK inhibitor (covalent and non-covalent) and a BCL-2 inhibitor. The main purpose of this study is to test if NX-5948 (bexobrutideg) works to treat patients with CLL/SLL. Participation could last up to 5 years, and possibly longer, if the disease does not progress.
详细描述
The main purpose of this study is to test if NX-5948 works to treat patients with R/R CLL/SLL. NX-5948 is a BTK degrader and works by destroying the BTK protein to stop all its actions. This is different from a BTK inhibitor which works by blocking only the kinase action of BTK. This study aims to answer these questions:
- How well does NX-5948 work to treat patients who have previously received a BTK inhibitor and a BCL-2 inhibitor?
- How safe is NX-5948 and can patients take NX-5948 as long as they need to?
- What is the amount of NX-5948 in the bloodstream over time when given to patients with CLL/SLL?
All patients in the study will receive NX-5948 orally until their cancer gets worse or if there are other reasons to stop taking NX-5948. Patients will have their cancer and other health check-ups regularly while they are taking NX-5948. If a patient's cancer has not gotten worse and they stop taking NX-5948, they will continue to have cancer check-ups until their cancer gets worse.
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
- •Age: ≥ 18 years
- •Confirmed relapsed/refractory CLL/SLL that meets iwCLL criteria for diagnosis and systemic treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Must have received a covalent BTK inhibitor (BTKi), a non-covalent BTKi, and a BCL-2 inhibitor either in separate lines of therapy or in combination; a line of therapy is considered 2 or more consecutive cycles of a systemic anti-CLL/SLL regimen
- •Participants with SLL must have measurable disease by radiographic assessment
- •Adequate organ and bone marrow function
- •Must sign an informed consent form indicating that he or she understands the purpose of the procedures required for the study and is willing to participate
排除标准
- •Known or suspected prolymphocytic leukemia or Richter's transformation before entering study
- •Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) before planned start of study drug
- •Antibody therapy must stop at least 4 weeks before the first dose of study drug
- •No other systemic anticancer therapy is allowed at the same time as this study; exception: continuation of hormonal therapy for breast and prostate cancer is allowed, if they are not on the list of prohibited concomitant medications in this study
- •Palliative limited-field radiotherapy within 7 days of the first dose of study or broad field radiotherapy within 28 days of first dose of study drug
- •Use of systemic corticosteroids >20 mg/day prednisone or equivalent within the 7 days before start of study drug except for those used as premedication for radio diagnostic contrast
- •Use of systemic immunosuppressive drugs other than systemic corticosteroids within 60 days before the first dose of study drug
- •Previously treated with a BTK degrader
- •Previous chimeric antigen receptor (CAR) T-cell therapy or allogeneic or autologous hematopoietic cell transplant within the past 90 days prior to enrollment
- •Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug
- •Note: Other Inclusion/Exclusion criteria may apply as defined in the protocol.
研究组 & 干预措施
NX-5948
干预措施: NX-5948 (Drug)
结局指标
主要结局
Objective response rate without partial response with lymphocytosis (PR-L) as determined by an Independent Review Committee (IRC)
时间窗: Up to approximately 5 years
The percentage of participants with response as determined according to 2018 International Workshop on CLL (iwCLL) guidelines. Response will include complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), and nodular PR.
次要结局
- Duration of response as determined by IRC and by investigator(Up to approximately 5 years)
- Progression-free survival as determined by IRC and by investigator(Up to approximately 5 years)
- Complete response rate as determined by IRC and by investigator(Up to approximately 5 years)
- Time to response as determined by IRC and by investigator(Up to approximately 5 years)
- Overall survival(Up to approximately 5 years)
- Number of participants with treatment-emergent adverse events (TEAEs), Grade 3 or higher TEAEs, serious adverse events, and TEAEs leading to study drug discontinuation(Up to approximately 3 years)
- Number of participants with clinically significant changes from baseline in laboratory parameters(Up to approximately 3 years)
- Number of participants with clinically significant changes from baseline in vital signs(Up to approximately 3 years)
- Pharmacokinetic profile of NX-5948(Up to approximately 1 year)
- Objective response rate with and without PR-L as determined by investigator(Up to approximately 5 years)
- Objective response rate with PR-L as determined by IRC(Up to approximately 5 years)
- Change from baseline in Global Health Status/Quality of Life on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline and up to approximately 5 years)
- Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)(Baseline and up to approximately 5 years)