Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 26
- 主要终点
- Minimal residual disease (MRD) negativity
研究概览
简要总结
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at high risk of developing Multiple Myeloma (MM), a group commonly labeled as High-Risk Smoldering Multiple Myeloma (HR-SMM).
The aim of the study is to understand the safety and tolerability (how the body reacts to linvoseltamab) as well as the effectiveness (how well linvoseltamab eliminates plasma cells and prevents the development of MM) of the study drug. There are 2 parts to the study.
- In Part 1, linvoseltamab will be given to a small number of participants to study the early side effects (safety) of the study drug and make sure the treatment is acceptable.
- In Part 2, linvoseltamab will be given to more participants to further assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat HR-SMM and prevent progression to MM.
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab (study drug) have improvement of their HR-SMM?
- What side effects may happen from taking the study drug?
- How much study drug is in the blood at different times?
- Whether the body makes antibodies against the study drug (which could make linvoseltamab less effective or could lead to side effects)
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •High-risk SMM diagnosis within 5 years of study enrollment, as described in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Adequate hematologic and hepatic function, as described in the protocol
- •Estimated glomerular filtration rate ≥30 mL/min/1.73 m^2
排除标准
- •Evidence of myeloma defining events *SLiM CRAB, as described in the protocol
- •*SLiM (greater than or equal to Sixty percent clonal plasma cells in the bone marrow, involved/uninvolved free Light chain ratio of ≥100 with the involved free light chain (FLC) being ≥100 mg/L, MRI with >1 focal lesion) CRAB (hyperCalcemia, Renal insufficiency, Anemia, or lytic Bone lesions)
- •Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma
- •Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
- •Any infection requiring hospitalization or treatment with intravenous anti-infectives within 28 days of first dose of study drug
- •Uncontrolled Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection, as described in the protocol
- •History of severe allergic reaction attributed to compounds with a similar chemical or biologic composition as the study drug or excipient
- •NOTE: Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Safety Run-In (Part 1)
Evaluation of initial safety and tolerability of the step-up regimen leading up to the start of full dose linvoseltamab.
干预措施: Linvoseltamab (Drug)
Expansion (Part 2)
Linvoseltamab monotherapy according to the same dosing schedule established in the safety run-in part.
干预措施: Linvoseltamab (Drug)
结局指标
主要结局
Minimal residual disease (MRD) negativity
时间窗: At 12 months
Frequency of adverse events of special interest (AESI) during the safety run-in observation period
时间窗: Up to 35 days
AESI include grade 2 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
Complete response (CR) as determined by the investigator
时间窗: Up to 7 years
Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period
时间窗: Up to 35 days
Severity of TEAEs during the safety run-in observation period
时间窗: Up to 35 days
MRD negativity
时间窗: At 24 months
Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period
时间窗: Up to 35 days
AESI include grade 2 or higher Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Frequency of Treatment-Emergent Adverse Events (TEAEs) during the safety run-in observation period
时间窗: Up to 35 days
Complete Response (CR) as determined by the investigator
时间窗: Up to 7 years
Minimal Residual Disease (MRD) negativity
时间窗: At 12 months
次要结局
- Frequency of TEAEs during expansion part(Up to 7 years)
- Frequency of laboratory abnormalities(Up to 7 years)
- Overall response of partial response (PR) or better(Up to 7 years)
- Duration of response (DOR)(Up to 7 years)
- Biochemical progression-free-survival (PFS)(Up to 7 years)
- Frequency of serious adverse events (SAEs)(Up to 7 years)
- Severity of SAEs(Up to 7 years)
- MRD negativity among participants that achieve very good partial response (VGPR) or better(Up to 3 years after end of treatment)
- Sustained MRD negativity(Up to 3 years after end of treatment)
- Severity of TEAEs during expansion part(Up to 7 years)
- Severity of laboratory abnormalities(Up to 7 years)
- Time from start of treatment to date of progression to MM or death(Up to 7 years)
- Time to initiation of first-line treatment for MM(Up to 7 years)
- Time from treatment initiation to date of any myeloma-defining event(Up to 7 years)
- Overall survival (OS)(Up to 7 years)
- Concentration of linvoseltamab in serum over time(Up to 2 years)
- Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time(Up to 2 years)
- Titer of ADAs to linvoseltamab over time(Up to 2 years)
- Overall response of Partial Response (PR) or better(Up to 7 years)
- Frequency of Serious Adverse Events (SAEs)(Up to 7 years)
- Duration Of Response (DOR)(Up to 7 years)
- Biochemical Progression-Free-Survival (PFS)(Up to 7 years)
- MRD negativity among participants that achieve Very Good Partial Response (VGPR) or better(Up to 3 years after end of treatment)
- Overall Survival (OS)(Up to 7 years)
- Concentration of linvoseltamab in serum(Up to 2 years)
- Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab(Up to 2 years)
- Magnitude of ADAs to linvoseltamab(Up to 2 years)