A Phase 1b, Open-Label Study of Eftozanermin Alfa (ABBV-621) in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 试验地点
- 19
- 主要终点
- Recommended Phase 2 Dose (RP2D) of Eftozanermin Alfa in Combination With Bortezomib and Dexamethasone (Safety Lead-In Arm)
研究概览
简要总结
Multiple myeloma (MM) is a rare cancer caused by abnormal survival of plasma cells (blood cells). Most trial participants with MM relapse (cancer has come back) or become non- responsive to treatment and remission gets shorter after each line of treatment. This is a study to determine recommended Phase 2 dose and change in disease symptoms of eftozanermin alfa in combination with bortezomib and dexamethasone to assess how efficient the treatment is in adult participants with relapsed/refractory (R/R) MM.
Eftozanermin alfa (ABBV-621) is an investigational drug being developed for the treatment of R/R Multiple Myeloma (MM). Study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. Participants in one arm will receive different doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine phase 2 dose (RP2D). Participants in the other arm will receive eftozanermin alfa at RP2D in combination with bortezomib and dexamethasone. Around 40 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 20 sites across the world.
Participants will receive eftozanermin alfa as an infusion into the vein in combination with bortezomib as an infusion into the vein or an injection under the skin and oral dexamethasone tablets for 12 cycles. Each cycle is 21 days for cycles 1-8 and 35 days for cycles 9-12.
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.
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
- •Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria.
- •Has measurable disease at screening, defined by at least 1 of the following:
- •Serum M-protein >= 1.0 g/dL (>= 10 g/L); OR
- •Urine M-protein >= 200 mg/24 hours; OR
- •Serum free light chain (sFLC) >= 10 mg/dL (100 mg/L), provided serum FLC ratio is abnormal.
- •Relapsed or refractory MM after receiving at least 3, but no more than 6 prior lines of therapy, including an immunomodulatory agent (IMiD), proteasome inhibitor (PI), and an anti-CD38 antibody, and has documented disease progression that occurred during or after the most recent therapy.
- •Has adequate hematologic, hepatic and renal function as defined in the protocol.
- •Eastern Cooperative Oncology Group (ECOG) 0 or
- •Life expectancy >= 12 weeks.
排除标准
- •Received bortezomib as part of the most recent prior therapy.
- •Has primary refractory disease defined as disease that is non-responsive.
- •Has not achieved a minimal response or better per IMWG criteria with any therapy.
- •Has discontinued bortezomib due to toxicity.
- •History of chronic liver disease or significant unresolved liver disease; currently active (within the last 6 months) hepatic impairment according to Child-Pugh Classification B or C.
- •History of cataract surgery within 6 months prior to study treatment and participant is not anticipated to have cataract surgery during the study treatment period (as assessed by ophthalmological exam at baseline).
- •Evidence of (as assessed by ophthalmological exam at baseline) uveitis, neovascular age related macular degeneration, retinal vein or artery occlusion and/or macular edema; no evidence of moderate or worsening diabetic retinopathy, retinal vascular disease or glaucoma (including participants with history of developing increased intraocular pressure after corticosteroid treatment) per clinical discretion of the consulting eye specialist.
- •Peripheral neuropathy Grade >= 2 or Grade 1 with pain.
- •Receipt of one of the following:
- •Corticosteroids at a dose equivalent to > 4 mg daily of dexamethasone or a single dose of > 40 mg of dexamethasone within 2 weeks prior to first dose.
- •Monoclonal antibodies used for multiple myeloma treatment within 4 weeks prior to first dose of study treatment.
- •Any other systemic therapies used for multiple myeloma treatment within 5 half-lives or 2 weeks prior to first dose, whichever is longer (or 2 weeks if half-life is unknown).
研究组 & 干预措施
Safety Lead-in
Participants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).
干预措施: Eftozanermin alfa (Drug)
Safety Lead-in
Participants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).
干预措施: Bortezomib (Drug)
Safety Lead-in
Participants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).
干预措施: Dexamethasone (Drug)
Dose Expansion
Participants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.
干预措施: Eftozanermin alfa (Drug)
Dose Expansion
Participants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.
干预措施: Bortezomib (Drug)
Dose Expansion
Participants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) of Eftozanermin Alfa in Combination With Bortezomib and Dexamethasone (Safety Lead-In Arm)
时间窗: Up to approximately 3 weeks after the first dose of study drug
RP2D of eftozanermin alfa in combination with bortezomib and dexamethasone will be determined.
Objective Response Rate (ORR) (Dose Expansion Arm)
时间窗: Up to approximately 44 weeks after the first dose of study drug
ORR is defined as percentage of participants with a response of partial response (PR) or better per International Myeloma Working Group (IMWG) criteria.
次要结局
- Rate of Very Good Partial Response (VGPR) or Better per IMWG Criteria(Up to approximately 44 weeks after the first dose of study drug)
- Electrocardiogram (ECG)(Up to approximately 44 weeks after the first dose of study drug)
- Duration of Response (DOR) for ORR(Up to approximately 44 weeks after the first dose of study drug)
- Number of Participants With Dose-Limiting Toxicities (DLTs)(Up to approximately 3 weeks after the first dose of study drug)
- Duration of Response (DOR) for VGPR or Better(Up to approximately 44 weeks after the first dose of study drug)
- Change in Vital Sign Measurements(Up to approximately 44 weeks after the first dose of study drug)
- Trough Concentration (Ctrough) of Eftozanermin Alfa(Up to Day 106)
- Antidrug Antibody (ADA)/Neutralizing Antibody (Nab) Assay(Up to approximately 44 weeks after the first dose of study drug)
- Number of Participants With Adverse Events (AEs)(Up to approximately 44 weeks after the first dose of study drug)
- Number of Participants With Abnormal Clinical Laboratory Test Results(Up to approximately 44 weeks after the first dose of study drug)
- Maximum Serum Concentration (Cmax) of Eftozanermin Alfa(Up to Day 8)