A Phase 1, First-in-Human, Open Label Study Evaluating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ABBV-438 in Adult Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 127
- 试验地点
- 12
- 主要终点
- Number of Participants With Adverse Events (AE)
研究概览
简要总结
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety, tolerability, and how ABBV-438 moves through the body, in adult participants with relapsed/refractory (R/R) MM. Adverse events, tolerability, how ABBV-438 moves through the body will be assessed.
ABBV-438 is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms broken into 2 parts. ABBV-438 will be given alone and multiple doses will be explored. This study will include a dose escalation phase (Part 1) to determine the best dose of ABBV-438, followed by a dose expansion phase (Part 2) to confirm the dose. Approximately 127 adult participants with R/R MM will be enrolled in the study in approximately 24 sites worldwide.
Participants will receive intravenous (IV) ABBV-438 alone first in multiple doses in the dose escalation phase (Part 1); then in 1 of 2 doses from Part 1 in the dose expansion phase (Part 2). The overall study duration will be approximately 69.5 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Has relapsed or refractory Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the standard International Myeloma Working Group (IMWG) (2016) response criteria:
- •Relapsed defined as previously treated myeloma that progresses and requires initiation of salvage therapy;
- •Refractory defined as disease that is nonresponsive (failure to achieve minimal response) while on last therapy, or progresses within 60 days of last therapy.
- •Has measurable disease at screening, defined by at least 1 of the following within 28 days prior to enrollment:
- •Serum M-protein >= 0.5 g/dL (>=5 g/L); OR;
- •Urine M-protein >= 200 mg/24 hours; OR;
- •Involved serum free light chain (sFLC) >= 10 mg/dL (100mg/L), provided serum FLC ratio is abnormal;
- •Must have had 3 or more prior lines of therapy with exposure to a proteasome inhibitor (PI), an immunomodulatory imide drugs (IMiD), and an anti-CD38 therapy and are intolerant to, or unable to access, available therapies that are known to confer clinical benefit to participants with relapsed or refractory (R/R) MM. Note: A line of therapy consists of relapsed or refractory 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.
排除标准
- •Known history of Central Nervous System involvement by MM.
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
研究组 & 干预措施
Part 2: ABBV-438 Monotherapy Dose Expansion (Dose A)
Participants will receive ABBV-438 Dose A alone, as part of the 69.5 study duration.
干预措施: ABBV-438 (Drug)
Part 1: ABBV-438 Monotherapy Dose Escalation
Participants will receive ABBV-438 in escalating doses alone, as part of the 69.5 study duration.
干预措施: ABBV-438 (Drug)
Part 2: ABBV-438 Monotherapy Dose Expansion (Dose B)
Participants will receive ABBV-438 Dose B alone, as part of the 69.5 study duration.
干预措施: ABBV-438 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AE)
时间窗: Up to Approximately 69.5 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.
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
时间窗: Up to Approximately 69.5 Months
Clinical laboratory parameters included tests of hematology and chemistry. The investigator will assess the results for clinical significance.
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters
时间窗: Up to Approximately 69.5 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 Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
时间窗: Up to Approximately 69.5 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 69.5 Months)
- Number of Participants Achieving VGPR or Better(Up to Approximately 69.5 Months)
- Duration of Response (DOR) in Participants who Achieved PR or VGPR or CR or sCR(Up to Approximately 69.5 Months)
- Progression-free survival (PFS)(Up to Approximately 69.5 Months)
- Overall survival (OS)(Up to Approximately 69.5 Months)
- Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-438(Up to Approximately 69.5 Months)
- Maximum Observed Plasma Concentration (Cmax) of ABBV-438(Up to Approximately 69.5 Months)
- Time to Cmax (Tmax) of ABBV-438(Up to Approximately 69.5 Months)
- t1/2 (Half-life) of ABBV-438(Up to Approximately 69.5 Months)