Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 116
- 试验地点
- 48
- 主要终点
- Frequency of Adverse Events Interest (AEI) during the safety observation period
研究概览
简要总结
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM).
The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of HR-MGUS and NHR-SMM.
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-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 the drug less effective or could lead to 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
- •HR-MGUS or NHR-SMM as defined 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 (GFR) ≥30 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) equation
排除标准
- •High-risk SMM, as defined in the protocol
- •Evidence of any of myeloma-defining events, as described in the protocol
- •Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
- •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 (IV) anti-infectives within 28 days of the first dose of linvoseltamab
- •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
- •NOTE: Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Safety Run-In (Part 1)
Sequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab.
干预措施: Linvoseltamab (Drug)
Expansion (Part 2) - Dose regimen 1
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
干预措施: Linvoseltamab (Drug)
Expansion (Part 2) - Dose regimen 2
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
干预措施: Linvoseltamab (Drug)
Expansion (Part 2) - Dose regimen 3
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
干预措施: Linvoseltamab (Drug)
Expansion (Part 2) - Dose regimen 4
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
干预措施: Linvoseltamab (Drug)
结局指标
主要结局
Frequency of Adverse Events Interest (AEI) during the safety observation period
时间窗: 35 days
Part 1 An AEI is a toxicity potentially related to study treatment that may preclude dose escalation or expansion according to the Bayesian Optimal Interval (BOIN) design decision rules
Frequency of Treatment-Emergent Adverse Event (TEAEs) during the safety observation period
时间窗: 35 days
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of TEAEs during the safety observation period
时间窗: 35 days
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Achievement of Complete Response (CR) as determined by the investigator
时间窗: Up to 5.5 years
Part 2
次要结局
- Frequency of TEAEs(Up to 5.5 years)
- Severity of TEAEs(Up to 5.5 years)
- Frequency of Serious Adverse Events (SAEs)(Up to 5.5 years)
- Severity of SAEs(Up to 5.5 years)
- Frequency of laboratory abnormalities(Up to 5.5 years)
- Severity of laboratory abnormalities(Up to 5.5 years)
- Minimal Residual Disease (MRD) negativity among participants that achieve a response of CR(Up to 5.5 years)
- Sustained MRD negativity on an annual basis(Up to 3 years after achievement of CR)
- Overall response of Partial Response (PR) or better as determined by the investigator(Up to 5.5 years)
- Duration Of Response (DOR) as determined by the investigator(Up to 5.5 years)
- Biochemical Progression-Free Survival (PFS) as determined by the investigator(Up to 5.5 years)
- Concentration of linvoseltamab in serum over time(Up to 9 months)
- Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab over the study duration(Up to 5.5. years)
- Magnitude of ADAs to linvoseltamab over the study duration(Up to 5.5. years)
研究者
Medical Affairs
Scientific
Regeneron Pharmaceuticals Inc.