First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants With 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
- 135
- 试验地点
- 74
- 主要终点
- Change in Laboratory Parameters
研究概览
简要总结
Non-Hodgkin's lymphoma (NHL) is a cancer that arises from the transformation of normal B and T lymphocytes (white blood cells). The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of ABBV-101 in adult participants in relapsed or refractory (R/R) non-Hodgkin's lymphomas: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large b-cell lymphoma (DLBCL), non-germinal center B cell (GCB) DLBCL, mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), or transformed indolent NHL. Adverse events will be assessed.
ABBV-101 is an investigational drug being developed for the treatment of NHL. This study will include a dose escalation phase to determine the maximum administered dose (MAD)/Maximum tolerated dose (MTD) of ABBV-101. Dose expansion part 2A will follow to further determine the safety and change in disease activity in participants with first line treatment (1L[non-US only]), second line or later of treatment (2L)+ CLL/SLL or third line or later of treatment (3L+) non-GCB DLBCL receiving ABBV-101 alone. Dose expansion Part 2B (non-US only) will follow to determine the safety and change in disease activity in participants with 1L or 2L+ CLL/SLL receiving ABBV-101 in combination with oral venetoclax. Approximately 390 adult participants with multiple NHL subtypes will be enrolled in the study in sites world wide.
In the dose escalation phase of the study participants will receive escalating oral doses of ABBV-101, until the MAD/MTD is determined, as part of the approximately 100 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101 alone or oral ABBV-101 at a dose determined in the dose escalation phase in combination with oral venetoclax, as part of the approximately 100 month study duration.
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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.
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
- •For Dose Escalation (Part 1) only (including backfill): Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have a documented diagnosis for one of the following third line or later B-cell malignancies, from one of the following world health organization (WHO)-defined histologies (Swerdlow et al 2016):
- •Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
- •For Dose Escalation (Part 1) backfill only - Bruton's tyrosine kinase inhibitor (BTKi)/Bruton's tyrosine kinase degrader (BTKd)-naïve CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received at least one prior systemic therapy that cannot be a BTK inhibitor or degrader, and, with the exception of BTK pathway agents, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment.
- •For Dose Escalation (Part 1) backfill only - BTKi/BCL-2i combination regimen-exposed 2L CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received one prior systemic therapy with a BTKi and BCL-2i combination regimen, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment.
- •Chimeric antigen receptor T-cells (CAR-T)/hematopoietic cell transplant (HCT) relapsed/refractory (R/R) or ineligible diffuse large b-cell lymphoma (DLBCL) from the following histologies: DLBCL not otherwise specified (NOS) (germinal center B cell [GCB] and non-GCB DLBCL), T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS.
- •Mantle cell lymphoma (MCL)
- •Follicular lymphoma [FL] (grades 1-3b)
- •Marginal zone lymphoma [MZL] (splenic, extranodal, and nodal)
- •Waldenström macroglobulinemia (WM)
- •Transformed indolent non-Hodgkin's lymphoma (iNHL)
- •For Dose Expansion (Part 2a) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL in their first-line or later treatment.
- •For Dose Expansion (Part 2a) DLBCL only: Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have documented diagnosis of CAR-T/HCT R/R or ineligible non-GCB DLBCL who are in their third line or later treatment with histology based on criteria established by the WHO.
- •For Dose Exploration of ABBV-101 combination with venetoclax (Part 2b) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL in their first-line or later treatment: In safety lead-in for each dose level, participants must have received at least one prior systemic therapy.
- •Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or
- •For EU only: Participant has an ECOG PS of 0 or
- •Participant has a life expectancy >= 12 weeks.
- •Prior Bruton's tyrosine kinase inhibitor (BTKi) is allowed.
- •Adequate hematologic, renal, and hepatic function per the protocol.
排除标准
- •Previously treated with a Bruton's tyrosine kinase (BTK) degrader.
- •Known active central nervous system (CNS) disease, or primary CNS lymphoma. Participants with prior CNS disease that have been effectively treated may be eligible.
- •Uncontrolled active systemic infection requiring systemic treatment that is ongoing or was completed <= 14 days before the first dose of study drug, or active cytomegalovirus infection.
研究组 & 干预措施
Part 2B: Dose Expansion ABBV-101 + Venetoclax in CLL/SLL
Participants with R/R and treatment-naive CLL/SLL will receive ABBV-101 at the dose determined in the dose escalation arm in combination with venetoclax, as part of the approximately 100 month study duration.
干预措施: ABBV-101 (Drug)
Part 1: Dose Escalation ABBV-101
Participants with relapsed or refractory (R/R) Non-Hodgkin's lymphoma (NHL) will receive escalating doses of ABBV-101, until the maximum administered dose (MAD)/Maximum tolerated dose (MTD) is determined, as part of the approximately 100 month study duration.
干预措施: ABBV-101 (Drug)
Part 2A: Dose Expansion ABBV-101 R/R non-GCB DLBCL
Participants with R/R non-germinal center B cell (GCB) diffuse large B-cell lymphoma (DLBCL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 100 month study duration.
干预措施: ABBV-101 (Drug)
Part 2B: Dose Expansion ABBV-101 + Venetoclax in CLL/SLL
Participants with R/R and treatment-naive CLL/SLL will receive ABBV-101 at the dose determined in the dose escalation arm in combination with venetoclax, as part of the approximately 100 month study duration.
干预措施: Venetoclax (Drug)
Part 2A: Dose Expansion ABBV-101 R/R & Treatment-Naive CLL/SLL
Participants with R/R and treatment-naive chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 100 month study duration.
干预措施: ABBV-101 (Drug)
结局指标
主要结局
Change in Laboratory Parameters
时间窗: Up to Approximately Two Years
Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
Change in Vital Signs
时间窗: Up to Approximately Two Years
Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
Change in Electrocardiogram (ECG)
时间窗: Up to Approximately Two Years
12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
Number of Participants with Adverse Events (AE)
时间窗: Up to Approximately 100 Months
AE is defined as 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.
次要结局
- Maximum Observed Serum Concentration (Cmax) of ABBV-101(Up to Approximately One Year)
- Time to Cmax (Tmax) of ABBV-101(Up to Approximately One Year)
- Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-101(Up to Approximately One Year)
- Number of Participants with Response of Partial Response (PR) or Better Response (Overall Response) per Disease-Specific Criteria(Up to Approximately Two Years)
- Duration of Response (DOR)(Up to Approximately Two Years)
- Maximum Observed Serum Concentration (Cmax) of Venetoclax(Up to Approximately One Year)
- Time to Cmax (Tmax) of Venetoclax(Up to Approximately One Year)
- Area Under the Serum Concentration Versus Time Curve (AUC) of Venetoclax(Up to Approximately One Year)