Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 149
- 试验地点
- 61
- 主要终点
- Severity of TEAEs
研究概览
简要总结
This study is researching an experimental drug called linvoseltamab (called "study drug"). The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy with autologous stem cell transplantation (transplant-eligible) or ineligible for autologous stem cell transplantation (transplant-ineligible).
The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM.
This study consists of 2 phases:
- In Phase 1 Parts A and B, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2.
- In Phase 1 Part C, the study drug will be given to participants to study the side effects when using different initial doses of the study drug.
- In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the activity of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM.
The study is looking at several research questions, including:
- What side effects may happen from taking linvoseltamab?
- What the right dosing regimen is for linvoseltamab?
- How many participants treated with linvoseltamab have improvement of their disease and for how long?
- The effects of linvoseltamab study treatment before and after transplant
- How much linvoseltamab is in the blood at different times?
- Whether the body makes antibodies against linvoseltamab (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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Confirmed diagnosis of symptomatic Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol
- •Response-evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol
- •No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
- •Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
- •Participants must be age <70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.
排除标准
- •Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
- •Known Central Nervous System (CNS) involvement with MM, known or suspected Progressive Multifocal Leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment
- •Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
- •Diagnosis of non-secretory MM, active plasma cell leukemia primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (Plasma cell dyscrasia with polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)
- •Note: Other protocol-defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Phase 2 - transplant ineligible cohort
Transplant-ineligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen until disease progression as per protocol.
干预措施: Linvoseltamab (Drug)
Phase 1 cohorts
Linvoseltamab dose escalation (part A), dose expansion (part B), and evaluation of alternative step-up regimen (part C) for participants with NDMM who are treatment-naïve.
干预措施: Linvoseltamab (Drug)
Phase 2 - transplant eligible cohort
Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol
干预措施: Linvoseltamab (Drug)
结局指标
主要结局
Severity of TEAEs
时间窗: Post-Last Linvoseltamab Dose, up to 90 days
Phase 1
Severity of AESIs
时间窗: Post-Last Linvoseltamab Dose, up to 90 days
Phase 1
Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
时间窗: Up to 5 years
Phase 2 Transplant-eligible cohort
Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
时间窗: Up to 5 years
Phase 2 Transplant-eligible cohort
Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
时间窗: Up to 5 years
Phase 2 Transplant-ineligible cohort
Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II
时间窗: Up to 5 years
Phase 2 Transplant ineligible cohort
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: End of the Observation period; up to day 28
Phase 1
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Post-Last Linvoseltamab Dose, up to 90 days
Phase 1
Incidence of Adverse Events of Special Interest (AESIs)
时间窗: Post-Last Linvoseltamab Dose, up to 90 days
Phase 1
Proportion of participants with a Very Good Partial Response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
时间窗: Up to 5 years
Phase 2
次要结局
- Incidence of TEAEs(Post-Last Linvoseltamab Dose, up to 90 days)
- MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician(Post-Last Linvoseltamab Dose, up to 90 days)
- PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician(Post-Last Linvoseltamab Dose, up to 90 days)
- Incidence of AESIs(Post-Last Linvoseltamab Dose, up to 90 days)
- PFS by risk levels(Post-Last Linvoseltamab Dose, up to 90 days)
- ORR by risk levels(Post-Last Linvoseltamab Dose, up to 90 days)
- Severity of TEAEs(Post-Last Linvoseltamab Dose, up to 90 days)
- ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician(Up to 5 years)
- Concentrations of Linvoseltamab in serum(Post-Last Linvoseltamab Dose, up to 12 weeks)
- Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria(Post-Last Linvoseltamab Dose, up to 90 days)
- Severity of AESIs(Post-Last Linvoseltamab Dose, up to 90 days)
- DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician(Post-Last Linvoseltamab Dose, up to 90 days)
- Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician(Post-Last Linvoseltamab Dose, up to 90 days)
- DOR by risk levels(Post-Last Linvoseltamab Dose, up to 90 days)
- Incidence of MRD-negative status(Up to 5 years)
- Time to neutrophil engraftment(Up to 100 days post-transplant)
- Time to platelet engraftment(Up to 100 days post-transplant)
- TTR by risk levels(Post-Last Linvoseltamab Dose, up to 90 days)
- PFS after ASCT followed by 3 cycles of linvoseltamab(Up to 5 years)
- Concentrations of total soluble B-Cell Maturation Antigen (BCMA)(Post-Last Linvoseltamab Dose, up to 12 weeks)
- Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab(Post-Last Linvoseltamab Dose, up to 30 days)
- Magnitude of ADAs to Linvoseltamab(Post-Last Linvoseltamab Dose, up to 30 days)
- Objective Response Rate (ORR) measured using the IMWG criteria(Up to 5 years)
- Duration Of Response (DOR) measured using the IMWG criteria(Post-Last Linvoseltamab Dose, up to 90 days)
- Progression-Free Survival (PFS) measured using the IMWG criteria(Post-Last Linvoseltamab Dose, up to 90 days)
- Time To Response (TTR) as measured using the IMWG criteria(Post-Last Linvoseltamab Dose, up to 90 days)
- MRD-negative status by risk levels(Post-Last Linvoseltamab Dose, up to 90 days)
- Cluster of Differentiation 34+ (CD34+) stem cell yield(At cycle 4 of induction (each cycle is 28 days long))