NCT05730036招募中3 期
An Open-label, Randomized, Phase 3 Study of Linvoseltamab (REGN5458; Anti- BCMA x Anti-CD3 Bispecific Antibody) Versus the Combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd), in Patients With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 410
- 试验地点
- 307
- 主要终点
- Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 antibody exposed participants
研究概览
简要总结
This study is researching an experimental drug called linvoseltamab, also called REGN5458.
Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after many other therapies had failed. These participants were no longer benefiting from standard medications and had no good treatment options. In that study, some participants who were treated with linvoseltamab had improvement of their myeloma (shrinkage of their tumors), including some participants who had complete responses (that is, the treatment got rid of all evidence of myeloma in their bodies).
This study is focused on participants who have multiple myeloma that has returned or needs to be treated again after one to four prior treatments and have standard cancer treatment options available to them. The aim of this study is to see how safe and effective linvoseltamab is compared to a combination of three cancer drugs: elotuzumab, pomalidomide and dexamethasone, (called EPd) in participants who have returned after having received prior treatment that included lenalidomide, a proteosome inhibitor, and (for participants in some countries) a cluster of differentiation 38 (CD38) antibody. Half of the participants in this study will get linvoseltamab, and the other half will get EPd.
This study is looking at several other research questions, including:
- How long participants benefit from receiving linvoseltamab compared with EPd
- How many participants treated with linvoseltamab or EPd have improvement of their multiple myeloma and by how much
- What side effects happen from taking linvoseltamab compared to EPd
- How long participants live while receiving treatment or after treatment with linvoseltamab compared to EPd
- If there is any improvement in pain after treatment with linvoseltamab compared to EPd
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age 18 years or older (or legal adult age in the country) at the time of the screening visit.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patients with ECOG 2 solely due to local symptoms of myeloma (eg. pain) may be allowed after discussion with the Medical Monitor.
- •Received at least 1 and no more than 4 prior lines of anti-neoplastic MM therapies, including lenalidomide and a proteasome inhibitor and demonstrated disease progression on or after the last therapy as defined by the 2016 IMWG criteria. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory, as described in the protocol.
- •Note: Participants in Israel also must have previously received a CD38 antibody. Participants in the EU and the UK must have previously received 2 to 4 prior lines of therapy, including a CD38 antibody.
- •Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol
- •Adequate hematologic function and hepatic function within 7 days of randomization, as well as adequate renal and cardiac function and corrected calcium
- •Life expectancy of at least 6 months
排除标准
- •Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- •Prior treatment with elotuzumab and/or pomalidomide
- •Participants with known MM brain lesions or meningeal involvement
- •Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
- •History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment. Participants who have received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. Steroids at doses equivalent to suppletion doses may be acceptable.
- •Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies Note: BCMA antibody-drug conjugates are allowed.
- •History of progressive multifocal leukoencephalopathy (PML), known or suspected PML, or history of a neurocognitive condition or central nervous system (CNS) movement disorder (Parkinson's disease or Parkinsonism).
- •Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug
- •Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); or another uncontrolled infection, as defined in the protocol 10 Cardiac ejection fraction <40%.
- •NOTE: Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Linvoseltamab
Experimental
Randomization 1:1
干预措施: Linvoseltamab (Drug)
Elotuzumab/Pomalidomide/Dexamethasone (EPd)
Active Comparator
Randomization 1:1
干预措施: Elotuzumab (Drug)
Elotuzumab/Pomalidomide/Dexamethasone (EPd)
Active Comparator
Randomization 1:1
干预措施: Pomalidomide (Drug)
Elotuzumab/Pomalidomide/Dexamethasone (EPd)
Active Comparator
Randomization 1:1
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 antibody exposed participants
时间窗: Up to approximatively 5 years
次要结局
- PFS per IMWG response criteria determined by IRC in all participants(Up to approximatively 5 years)
- Objective Response (OR) of Complete Response (CR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants(Up to approximatively 5 years)
- OR of CR or better per IMWG response criteria as determined by IRC in all participants(Up to approximatively 5 years)
- Overall Survival (OS) in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- OS in all participants(Up to approximatively 5 years)
- Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Incidence of MRD negative status in all participants(Up to approximatively 5 years)
- Mean change in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3 in participants previously exposed to CD38 antibodies(Baseline to week 12)
- Mean change in the worst pain score measured by BPI-SF Item 3 in all participants(Baseline to week 12)
- Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Incidence TEAEs in all participants(Up to approximatively 5 years)
- Severity of TEAEs in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Severity of TEAEs in all participants(Up to approximatively 5 years)
- Incidence of adverse events of special interest (AESI) in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Incidence of AESI in all participants(Up to approximatively 5 years)
- Severity of AESI in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Severity AESI in all participants(Up to approximatively 5 years)
- Incidence of Serious Adverse Events (SAE) in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Incidence of SAE in all participants(Up to approximatively 5 years)
- Severity of SAE in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Severity of SAE in all participants(Up to approximatively 5 years)
- PFS per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- PFS per IMWG response criteria as determined by the investigator in all participants(Up to approximatively 5 years)
- OR of Partial Response (PR) or better per IMWG response criteria as determined by the IRC in CD38 antibody exposed participants(Up to approximatively 5 years)
- OR of PR or better per IMWG response criteria as determined by the IRC in all participants(Up to approximatively 5 years)
- OR of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants(Up to approximatively 5 years)
- OR of VGPR or better per IMWG response criteria as determined by IRC in all participants(Up to approximatively 5 years)
- OR of PR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- OR of PR or better per IMWG response criteria as determined by the investigator in all participants(Up to approximatively 5 years)
- OR of VGPR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- OR of VGPR or better per IMWG response criteria as determined by the investigator in all participants(Up to approximatively 5 years)
- OR of CR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- OR of CR or better per IMWG response criteria as determined by the investigator in all participants(Up to approximatively 5 years)
- Duration of Response (DoR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- DoR as per IMWG response criteria as determined by the investigator in all participants(Up to approximatively 5 years)
- DoR as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- DoR as per IMWG response criteria as determined by the IRC in all participants(Up to approximatively 5 years)
- Duration of MRD negative status in the bone marrow in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Duration of MRD negative status in the bone marrow in all participants(Up to approximatively 5 years)
- Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in all participants(Up to approximatively 5 years)
- Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in all participants(Up to approximatively 5 years)
- Concentration of linvoseltamab in the serum over time in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Concentration of linvoseltamab in the serum over time in all participants(Up to approximatively 5 years)
- Incidence of antidrug antibodies (ADAs) in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Incidence of ADAs in all participants(Up to approximatively 5 years)
- Titer of ADAs in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Titer of ADAs in all participants(Up to approximatively 5 years)
- Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time in participants previously exposed to CD38 antibodies(Up to approximatively 5 years)
- Incidence of Nabs to linvoseltamab over time in all participants(Up to approximatively 5 years)
- Proportion of Pain Responders in participants previously exposed to CD38 antibodies(At week 12)
- Proportion of Pain Responders in all participants(At week 12)
- Change in patient-reported global health status/quality of life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in participants previously exposed to CD38 antibodies(Baseline to week 12)
- Change in patient-reported QoL, per EORTC QLQ-C30 in all participants(Baseline to week 12)
- Change in patient reported disease symptoms per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20]) in participants previously exposed to CD38 antibodies(Baseline to week 12)
- Change in patient reported disease symptoms per EORTC QLQ-MY20 in all participants(Baseline to week 12)
- Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS) in participants previously exposed to CD38 antibodies(Baseline to week 12)
- Patient-Reported Outcomes in PGIS in all participants(Baseline to week 12)
- Patient-Reported Outcomes in Patient Global Impression of Change (PGIC) in participants previously exposed to CD38 antibodies(Baseline to week 12)
- Patient-Reported Outcomes in PGIC in all participants(Baseline to week 12)
- Change in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) in participants previously exposed to CD38 antibodies(Baseline to week 12)
- Change in patient-reported general health status per EQ-5D-5L in all participants(Baseline to week 12)
研究者
研究点 (307)
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