A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of T Cell Engaging Bi/Tri-specific Antibodies in Subjects With MM
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 602
- 试验地点
- 53
- 主要终点
- Number of Participants with Adverse Events (AE)s
研究概览
简要总结
Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine the safety, efficacy, and pharmacokinetics of Etentamig and ABBV-2001 in adult participants with MM.
Etentamig and ABBV-2001 are investigational drugs being developed for the treatment of MM. This study is broken into 6 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants in substudies 1-4 will receive escalating doses of etentamig alone or with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R), followed by etentamig at the dose levels established during the escalation phases alone or with DR, Kd, R. Participants in substudies 1-4 can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Participants in substudies 5-6 will receive escalating doses or at the dose levels established during the escalation phases of ABBV-2001 with iberdomide or mezigdomide. Around 602 adult participants with MM will be enrolled at approximately 75 sites worldwide
In substudies 1-3, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or with IV and DRd, DKd, or R. In substudie 4, participants will receive escalating doses of etentamig as Intravenous (IV) infusions followed by IV infusions of etentamig at the dose levels established during the escalation phase. In substudies 5-6, participants will receive escalating doses of ABBV-2001 as subcutaneous (SC) injections, with oral iberdomide or mezigdomide, followed by SC injections of ABBV-2001 at the dose levels established during the escalation phases with oral iberdomide or mezigdomide. The study duration is approximately 130 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. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Eastern cooperative oncology group (ECOG) performance of <=
- •Confirmed diagnosis of multiple myeloma (MM) according to the International Myeloma Working Group (IMWG) diagnostic criteria with either newly diagnosed or relapsed or refractory (RR) MM, depending on the substudy.
排除标准
- •Participant who has known active central nervous system involvement of MM.
- •Participant who has known active infection as outlined in the protocol.
研究组 & 干预措施
Substudy 2: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 3: Comparator
Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration.
干预措施: Daratumumab (Drug)
Substudy 5: ABBV-2001 Dose Escalation
Participants will receive escalating ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.
干预措施: ABBV-2001 (Drug)
Substudy 1: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 2: Etentamig Dose Escalation
Participants will receive escalating etentamig, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 3: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 4: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with R, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 2: Comparator
Participants will receive lenalidomide (R), as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 3: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 3: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration.
干预措施: Dexamethasone (Drug)
Substudy 3: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with carfilzomib, and dexamethasone (Kd), as part of the approximately 130 month study duration.
干预措施: Carfilzomib (Drug)
Substudy 3: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 3: Comparator
Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration.
干预措施: Dexamethasone (Drug)
Substudy 4: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with R, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 5: ABBV-2001 Dose Expansion Dose Level 1
Participants will receive dose level 1 of ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.
干预措施: ABBV-2001 (Drug)
Substudy 4: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with R, as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 5: ABBV-2001 Dose Expansion Dose Level 2
Participants will receive dose level 2 of ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.
干预措施: ABBV-2001 (Drug)
Substudy 6: ABBV-2001 Dose Escalation
Participants will receive escalating ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.
干预措施: ABBV-2001 (Drug)
Substudy 6: ABBV-2001 Dose Expansion Dose Level 1
Participants will receive dose level 1 of ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.
干预措施: ABBV-2001 (Drug)
Substudy 6: ABBV-2001 Dose Expansion Dose Level 2
Participants will receive dose level 2 of ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.
干预措施: ABBV-2001 (Drug)
Substudy 1: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration.
干预措施: Daratumumab (Drug)
Substudy 1: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 1: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 1: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with daratumumab, and lenalidomide (DR), as part of the approximately 130 month study duration.
干预措施: Daratumumab (Drug)
Substudy 1: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 1: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with DR, as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 1: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 1: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with DR, as part of the approximately 130 month study duration.
干预措施: Daratumumab (Drug)
Substudy 1: Comparator
Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 1: Comparator
Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration.
干预措施: Dexamethasone (Drug)
Substudy 1: Comparator
Participants will receive daratumumab, lenalidomide, and dexamethasone (DRd), as part of the approximately 130 month study duration.
干预措施: Daratumumab (Drug)
Substudy 2: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 3: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration.
干预措施: Dexamethasone (Drug)
Substudy 3: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with Kd, as part of the approximately 130 month study duration.
干预措施: Carfilzomib (Drug)
Substudy 3: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration.
干预措施: Dexamethasone (Drug)
Substudy 3: Etentamig Dose Expansion Dose Level 2
Participants will receive dose level 2 of etentamig in combination with Kd, as part of the approximately 130 month study duration.
干预措施: Carfilzomib (Drug)
Substudy 3: Comparator
Participants will receive daratumumab, carfilzomib, and dexamethasone (DKd), as part of the approximately 130 month study duration.
干预措施: Carfilzomib (Drug)
Substudy 4: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with R, as part of the approximately 130 month study duration.
干预措施: Etentamig (Drug)
Substudy 4: Etentamig Dose Escalation
Participants will receive escalating etentamig in combination with R, as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 4: Etentamig Dose Expansion Dose Level 1
Participants will receive dose level 1 of etentamig in combination with R, as part of the approximately 130 month study duration.
干预措施: Lenalidomide (Drug)
Substudy 5: ABBV-2001 Dose Escalation
Participants will receive escalating ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.
干预措施: Iberdomide (Drug)
Substudy 5: ABBV-2001 Dose Expansion Dose Level 1
Participants will receive dose level 1 of ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.
干预措施: Iberdomide (Drug)
Substudy 5: ABBV-2001 Dose Expansion Dose Level 2
Participants will receive dose level 2 of ABBV-2001 in combination with iberdomide, as part of the approximately 130 month study duration.
干预措施: Iberdomide (Drug)
Substudy 6: ABBV-2001 Dose Escalation
Participants will receive escalating ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.
干预措施: Mezigdomide (Drug)
Substudy 6: ABBV-2001 Dose Expansion Dose Level 1
Participants will receive dose level 1 of ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.
干预措施: Mezigdomide (Drug)
Substudy 6: ABBV-2001 Dose Expansion Dose Level 2
Participants will receive dose level 2 of ABBV-2001 in combination with mezigdomide, as part of the approximately 130 month study duration.
干预措施: Mezigdomide (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AE)s
时间窗: Up to Approximately 130 Months
An adverse event 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.
Substudy 1: Dose-Limiting Toxicity (DLT) of Etentamig + Daratumumab and Lenalidomide (DR) in Participants with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TI NDMM)
时间窗: Up to Approximately 8 weeks
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Substudy 2: DLT of Etentamig Monotherapy as Maintenance in Participants with Transplant-Eligible Newly Diagnosed Multiple Myeloma (TE NDMM)
时间窗: Up to Approximately 8 Weeks
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Substudy 3: DLT of Etentamig +Carfilzomib and Dexamethasone (Kd) Combination in Participants with Relapsed or Refractory Multiple Myeloma (RR MM)
时间窗: Up to Approximately 8 Weeks
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Substudy 4: DLT of Etentamig plus Lenalidomide when Given as Maintenance in Participants with TE NDMM
时间窗: Up to Approximately 8 Weeks
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Substudy 5: DLT of ABBV-2001 in Combination with Iberdomide in Participants with RR MM
时间窗: Up to Approximately 8 Weeks
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Substudy 6: DLT of ABBV-2001 in Combination with Mezigdomide in Participants with RR MM
时间窗: Up to Approximately 8 Weeks
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
次要结局
- Substudy 1, 2, 3, 4: Complete Response Rate(Up to Approximately 1 Year)
- Substudy 1, 2, 3, 4: Overall Response Rate (ORR)(Up to Approximately 1 Year)
- Substudy 1, 2, 3, 4: Progression Free Survival (PFS)(Up to Approximately 130 Months)
- Substudy 1, 2, 3, 4: Duration of Response (DOR)(Up to Approximately 130 Months)
- Substudy 1, 2, 3, 4: Time-to-Progression (TTP)(Up to Approximately 130 Months)
- Substudy 1, 2, 3, 4: Minimal Residual Disease (MRD) negativity(Up to Approximately 52 Weeks)
- Substudy 1, 2, 3, 4, 5, 6: Complete Response Rate(Up to Approximately 1 Year)
- Substudy 1, 2, 3, 4, 5, 6: Overall Response Rate (ORR)(Up to Approximately 1 Year)
- Substudy 1, 2, 3, 4, 5, 6: Progression Free Survival (PFS)(Up to Approximately 130 Months)
- Substudy 1, 2, 3, 4, 5, 6: Duration of Response (DOR)(Up to Approximately 130 Months)
- Substudy 1, 2, 3, 4, 5, 6: Time-to-Progression (TTP)(Up to Approximately 130 Months)
- Substudy 1, 2, 3, 4, 5, 6: Minimal Residual Disease (MRD) negativity(Up to Approximately 52 Weeks)