A First-in-Human Study of ABBV-525 (MALT1 Inhibitor) in B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 78
- 试验地点
- 69
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of ABBV-525
研究概览
简要总结
B-cell malignancies are a group of cancers of B lymphocytes, a type of white blood cell responsible for fighting infections. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-525 as a monotherapy.
ABBV-525 is an investigational drug being developed for the treatment of B-Cell Malignancies. Study doctors put the participants in groups called treatment arms. Participants will receive ABBV-525 at different doses. Approximately 150 adult participants will be enrolled in the study across sites worldwide.
In part 1 (dose escalation), participants will receive escalating oral doses of ABBV-525. In part 2 (dose optimization), participants will receive one of two oral doses of ABBV-525, until the recommended phase 2 dose (RP2D) is determined. In part 3 (dose expansion), participants will receive the RP2D oral dose of ABBV-525. The estimated duration of the study is up to 64 months.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.
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
- •Dose Escalation (Part 1) Only: Participants with a documented diagnosis of one of the following third line or later of treatment (3L)+ mature B-cell malignancies, from the World Health Organization (WHO)-defined histologies as defined in the protocol.
- •Dose Optimization (Part 2) Only: Participants with documented diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with histology based on WHO criteria, with measurable disease requiring treatment as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL).
- •Dose Expansion (Part 3) Only: Participants with documented diagnosis of one of the 3L+ mature B-cell malignancies based on WHO criteria listed in the protocol, with measurable disease requiring treatment.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or
- •Participant has a life expectancy >= 12 weeks.
- •Adequate hematological and hepatic function as defined in the protocol.
- •Must have archival or freshly collected tumor tissue for correlative studies before study enrollment.
- •Participants with prior central nervous system (CNS) disease that has been effectively treated may be eligible.
- •Participants with resolved coronavirus disease 2019 (COVID-19) infection are eligible.
排除标准
- •Known active CNS disease, or primary CNS lymphoma.
- •Known bleeding disorders.
- •Known history of stroke or intracranial hemorrhage within 12 months prior to first dose of study treatment.
- •Uncontrolled active systemic infection, or active cytomegalovirus infection.
- •Active and/or chronic hepatitis B or C infection and/or the criteria listed in the protocol.
- •Known history of human immunodeficiency virus (HIV).
- •Known active COVID-19 infection. Participant must not have signs/symptoms associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 infection during screening. If participant has signs/symptoms suggestive of COVID-19 infection, the participant must have a negative molecular (e.g., polymerase chain reaction) test or 3 negative antigen test results at least 24 hours apart.
研究组 & 干预措施
ABBV-525 Dose Escalation
Participants will receive escalating doses of ABBV-525 until doses for optimization are determined, as part of an approximately 64 month study period.
干预措施: ABBV-525 (Drug)
ABBV-525 Dose Optimization
Participants will receive one of two doses of ABBV-525 until the recommended phase 2 dose (RP2D) is determined, as part of an approximately 64 month study period.
干预措施: ABBV-525 (Drug)
ABBV-525 Dose Expansion
Participants will receive the RP2D dose of ABBV-525, as part of an approximately 64 month study period.
干预措施: ABBV-525 (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of ABBV-525
时间窗: Up to 12 Months
Maximum observed plasma concentration of ABBV-525.
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters
时间窗: Up to Approximately 64 Months
Vital sign parameters included body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate. The investigator will assess the results for clinical significance.
Number of Participants With Dose-Limiting Toxicities (DLT)
时间窗: Up to Approximately 28 Days
A DLT is defined as any AE for which a clear alternative cause cannot be established (eg, attributed to the disease under study, another disease, or to a concomitant medication by the study investigators or medical monitor).
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
时间窗: Up to Approximately 64 Months
Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator will assess the results for clinical significance.
Number of Participants With Adverse Events (AE)
时间窗: Up to Approximately 64 Months
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is defined as any untoward medical occurrence, whether associated with study drug or not, that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event requiring medical or surgical intervention to prevent serious outcome.
Time to Cmax (Tmax) of ABBV-525
时间窗: Up to 12 Months
Time to Cmax of ABBV-525.
Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525
时间窗: Up to 12 Months
Area under the plasma concentration-time curve of ABBV-525.
Number of Tumor Lysis Syndrome (TLS)
时间窗: Up to Approximately 64 Months
TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
时间窗: Up to Approximately 64 Months
A standard 12-lead ECG will be performed. The investigator will assess the results for clinical significance.
次要结局
- Overall Response Rate (ORR)(Up to Approximately 64 Months)
- Duration of Response (DOR)(Up to Approximately 64 Months)