A Phase 1/2, Dose Escalation, Safety and Tolerability Study of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 14
- 主要终点
- Recommended Phase 2 Dose (Phase 1)
研究概览
简要总结
This is a Phase 1/2 study designed to evaluate the safety and tolerability of BION-1301 in adults with relapsed or refractory multiple myeloma whose disease has progressed after 3 or more prior systemic therapies.
详细描述
An open-label, multi-center, dose-selection Phase 1/2 study (also referred to as ADU-CL-16) evaluating BION-1301, a humanized monoclonal antibody directed against APRIL for the treatment of relapsed or refractory MM. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and initial clinical activity of BION-1301 administered as a single agent.
The study will be conducted in 2 parts. Phase 1 is dose escalation and seeks to determine the recommended phase 2 dose (RP2D). Once an RP2D is identified, Phase 2 of the study will open and continue to evaluate the safety and preliminary efficacy of BION-1301 administered at selected dose level(s).
The population for this study will consist of adults with relapsed or refractory MM whose disease has progressed after at least 3 prior systemic therapies. BION-1301 will be administered in 28-day cycles; the dosing interval will be once every two weeks (Q2W).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Individuals eligible to participate in this study must meet the following key criteria and additional criteria as specified in the protocol:
- •Male or female, aged ≥ 18 years
- •Confirmed diagnosis of MM per IMWG criteria
- •Measurable disease as defined by one or more of the following:
- •Serum M-protein ≥ 0.5 g/dL
- •Urine M-protein ≥ 200 mg/24 hours
- •Serum Free Light Chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal
- •In cases where SPEP is unreliable, serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL) is acceptable
- •Relapsed or refractory (Rajkumar, 2011) to 3 or more different prior lines of therapy for MM, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), chemotherapies, or monoclonal antibodies, and not a candidate for, or intolerant to established therapy known to provide clinical benefit.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1
- •Adequate organ and marrow function at Screening, as defined by the study protocol.
排除标准
- •Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, Waldenstrom's macroglobulinemia, or IgM myeloma
- •Active plasma cell leukemia (˃ 2.0 × 109/L circulating plasma cells by standard differential)
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Prior treatment directed to B-cell Activating Factor (BAFF; BLyS), B-cell Maturation Antigen (BCMA;TNFSF17) or Transmembrane Activator and CAML interactor (TACI; TNFSF13B), including antibodies or BCMA- or TACI-directed Chimeric Antigen Receptor (CAR)-T cell therapy
结局指标
主要结局
Recommended Phase 2 Dose (Phase 1)
时间窗: Approximately 2 years
Recommended Phase 2 Dose RP2D of BION-1301 when administered as a single-agent
Biomarkers (Phase 1 and 2)
时间窗: Baseline and approximately 2 years
Biomarkers such as soluble a proliferation inducing ligand (APRIL; TNFSF13); soluble B cell maturation antigen (BCMA; TNFRSF17)
Safety Profile (Phase 2)
时间窗: 28 days
BION-1301 safety profile based on incidence of TEAEs (treatment emergent adverse events), changes in safety parameters, and unacceptable toxicities
Progression-Free Survival (Phase 2)
时间窗: Approximately 30 months
Progression-free survival (PFS) defined as time from first dose of study drug to date of first tumor progression or death due to any cause
Safety (Phase 1)
时间窗: 28 days following first administration of BION-1301
Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities (DLTs) of BION-1301 as a single agent
Bioanalytical Measures (Phase 1 and Phase 2)
时间窗: Baseline and approximately 2 years
Relative change in serum and urine M-protein levels defined as the maximum reduction from baseline
Response Rate (Phase 2)
时间窗: Approximately 30 months
Objective response rate (ORR) based on International Myeloma Working Group (IMWG) uniform response criteria of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)
Overall Survival (Phase 2)
时间窗: Approximately 30 months
Overall survival (OS) defined as the time from first dose of study drug to date of death due to any cause
次要结局
未报告次要终点