A Phase 1 First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of ABBV-623 and ABBV-992 in Subjects With B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 5
- 主要终点
- Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL
研究概览
简要总结
B-cell cancer is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The main objective of this study is to evaluate the safety and efficacy of ABBV-623 and ABBV-992 given alone and in combination in treating B-cell cancers. Adverse events, change in disease activity and how the drug moves through the body of adult participants with B-cell cancers will be evaluated.
ABBV-623 and ABBV-992 are investigational drugs being developed for the treatment of B-cell cancer. Study doctors assign participants to one of six groups, called treatment arms. Approximately 105 adult participants with a diagnosis of B-cell cancer will be enrolled in the study at approximately 50 sites worldwide.
Participants in the combination expansion treatment arms will receive oral tablets of ABBV-623 and/or ABBV-992 once daily for 24 months. All other arms are treated until progression.
Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be evaluated by medical assessments and blood tests. Adverse events will be collected and assessed throughout the clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Participants must have documented diagnosis for one of the following B-cell malignancies: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), with measurable disease requiring treatment.
- •Participants have relapsed or refractory to at least 2 prior systemic therapies.
- •Combination Dose Expansion Only: Participants with documented diagnosis of CLL/SLL with measurable disease requiring treatment per by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •CLL/SLL, MCL, WM, MZL only: Prior Bruton's tyrosine kinase inhibitor (BTKi) exposure will be allowed if participant did not progress on active treatment and there is no evidence of resistance mutations.
- •Renal, liver and hematological function lab values as determined in the protocol.
- •For participants with prior BTK inhibitor exposure, no evidence of mutations which confer resistance to covalent BTK inhibitors.
排除标准
- •Participants with indolent forms of non-Hodgkin lymphoma (NHL) that require immediate cytoreduction.
- •Participants with prior B-cell lymphoma 2 (BCL2) inhibitor (BCL2i) exposure (except for participants in the ABBV-992 monotherapy cohort).
研究组 & 干预措施
Monotherapy in Dose Escalation: ABBV-623
Participants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.
干预措施: ABBV-623 (Drug)
Monotherapy in Dose Escalation: ABBV-992
Participants with R/R B-cell malignancies will receive escalating doses of ABBV-992.
干预措施: ABBV-992 (Drug)
Combination in Dose Escalation
Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.
干预措施: ABBV-623 (Drug)
Combination in Dose Escalation
Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.
干预措施: ABBV-992 (Drug)
Monotherapy in Dose Expansion: ABBV-623
Participants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
干预措施: ABBV-623 (Drug)
Monotherapy in Dose Expansion: ABBV-992
Participants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
干预措施: ABBV-992 (Drug)
Combination in Dose Expansion
Participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) will receive ABBV-623 and ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
干预措施: ABBV-623 (Drug)
Combination in Dose Expansion
Participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) will receive ABBV-623 and ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.
干预措施: ABBV-992 (Drug)
结局指标
主要结局
Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL
时间窗: Up to approximately 2 years
ORR is the proportion of R/R CLL/SLL participants achieving a response of PR or better per IWCLL without the use of new anti-cancer therapy.
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992
时间窗: Up to approximately 96 weeks
The area under the plasma concentration-time curve (AUC; measured in h\*ng/mL/mg) is a method of measurement of the total exposure of ABBV-992 in blood plasma.
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623
时间窗: Up to approximately 96 weeks
The area under the plasma concentration-time curve (AUC; measured in h\*ng/mL/mg) is a method of measurement of the total exposure of ABBV-623 in blood plasma.
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992
时间窗: Up to approximately 96 weeks.
The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-992 achieves in the blood after administration in a dosing interval.
Percentage of Participants With Adverse Events (AEs)
时间窗: Up to approximately 25 months.
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623
时间窗: Up to approximately 96 weeks
The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-623 achieves in the blood after administration in a dosing interval.
次要结局
- Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better(Up to approximately 2 years)
- Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better(Up to approximately 2 years)
- Combination Dose Expansion in Participants With CLL/SLL: Time to Response(Up to approximately 2 years)
- Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival(Approximately 2 years after study drug discontinuation)
- Dose Escalation in Participants With R/R B-cell Malignancies: Percentage of Participants Achieving a Response of Partial Response (PR) or Better per Disease-Specific Response Criteria (e.g., IWCLL, Lugano, IWWM)(Up to approximately 2 years)
- Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)(Up to approximately 2 years)
- Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better(Up to approximately 2 years)
- Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)(Up to approximately 2 years)
- Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD(Up to approximately 96 weeks)
- Combination Dose Expansion in Participants With CLL/SLL: Overall Survival(Approximately 2 years after study drug discontinuation)
- Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better(Up to approximately 2 years)
- Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)(Up to approximately 1 Year)