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
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 76
- 试验地点
- 16
- 主要终点
- Phase 1: Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
For Phase 1: • To assess the safety, tolerability, and to determine a recommended phase 2 dose regimen (RP2DR) of linvoseltamab for phase 2 of the study
For Phase 2:
• To assess the preliminary anti-tumor activity of linvoseltamab in participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) (transplant-eligible) • To assess the preliminary anti-tumor activity of linvoseltamab in participants with NDMM who are ineligible for ASCT (transplant-ineligible)
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Phase 2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 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
- •Measurable disease, 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 Exclusion criteria apply
结局指标
主要结局
Phase 1: Incidence of dose-limiting toxicities (DLTs)
Phase 1: Incidence of dose-limiting toxicities (DLTs)
Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
Phase 1: Severity of treatment-emergent adverse events (TEAEs)
Phase 1: Severity of treatment-emergent adverse events (TEAEs)
Phase 1: Incidence of adverse events of special interest (AESIs)
Phase 1: Incidence of adverse events of special interest (AESIs)
Phase 1: Severity of adverse events of special interest (AESIs)
Phase 1: Severity of adverse events of special interest (AESIs)
Phase 2: Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
Phase 2: Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
Phase 2 Transplant-eligible cohort: Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
Phase 2 Transplant-eligible cohort: Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
Phase 2 Transplant-eligible cohort: Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
Phase 2 Transplant-eligible cohort: Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
Phase 2 Transplant-ineligible cohort: Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
Phase 2 Transplant-ineligible cohort: Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
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
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
次要结局
- Phase 1 and 2: Concentrations of Linvoseltamab in serum
- Phase 1 and 2: Concentrations of total soluble B-cell maturation antigen (BCMA)
- Phase 1 and 2: Incidence of anti-drug antibodies (ADAs) to Linvoseltamab
- Phase 1 and 2: Titer of ADAs to Linvoseltamab
- Phase 1: Objective response rate (ORR) measured using the IMWG criteria
- Phase 1: Duration of Response (DOR) measured using the IMWG criteria
- Phase 1: Progression-free survival (PFS) measured using the IMWG criteria
- Phase 1: Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria
- Phase 2: Incidence of treatment-emergent adverse events (TEAEs)
- Phase 2: Severity of TEAEs
- Phase 2: Incidence of adverse events of special interest (AESIs)
- Phase 2: Severity of AESIs
- Phase 2: ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
- Phase 2: MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician
- Phase 2: DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
- Phase 2: PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician
- Phase 2: Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician
- Phase 2: Time to response (TTR) as measured using the IMWG criteria
- Phase 2: ORR by risk levels
- Phase 2: MRD-negative status by risk levels
- Phase 2: DOR by risk levels
- Phase 2: TTR by risk levels
- Phase 2: PFS by risk levels
- Phase 2: Incidence of MRD-negative status
- Phase 2 Transplant-eligible cohort: Cluster of differentiation 34+ (CD34+) stem cell yield
- Phase 2 Transplant-eligible cohort: Time to neutrophil engraftment
- Phase 2 Transplant-eligible cohort: Time to platelet engraftment
- Phase 2 Transplant-eligible cohort: PFS after ASCT followed by 3 cycles of linvoseltamab
研究者
Medical Affairs
Scientific
Regeneron Pharmaceuticals Inc.