NCT05137054招募中1 期
Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 317
- 试验地点
- 82
- 主要终点
- Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
研究概览
简要总结
This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again.
In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies).
This study is the first time linvoseltamab will be combined with other cancer therapies.
The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination.
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma
- What side effects may happen from taking linvoseltamab together with another cancer treatment
- How much study drug is in the blood at different times
- Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) 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
- •General Key Inclusion Criteria:
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Participants must have measurable disease as defined in the protocol according to IMWG consensus criteria
- •Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
- •Life expectancy of at least 6 months
- •Cohort Specific Inclusion Criteria:
- •For cohorts 1-6, each participant must have RRMM with progression following at least 3 lines of therapy, or at least 2 lines of therapy and either prior exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD) and 1 Proteasome Inhibitor (PI), or double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated, as described in the protocol Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated, as described in the protocol
- •Cohort 7 and 8:
- •For participants without measurable disease by biochemical parameters [serum or urine M-protein, or serum involved Free Light Chain (FLC)], presence of at least 1 soft tissue plasmacytoma with a single diameter of ≥2 cm
- •RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI or triple-class refractory disease (anti-CD38 antibody, IMiD, PI) Cohort 9: Progressive RRMM in participants with triple-class refractory disease (anti-CD38 antibody, IMiD, PI) after at least 3 lines of therapy Cohort 10: Progressive RRMM after at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI
- •General Key
排除标准
- •Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)
- •Participants with known MM brain lesions or meningeal involvement
- •Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter
- •History of allogeneic and autologous stem cell transplantation, as described in the protocol
- •Unless stated otherwise in a specific sub-protocol, prior treatment with a T cell-based immunotherapy directed against B-Cell Maturation Antigen (BCMA) bispecific antibodies and Bispecific T-cell Engagers (BiTEs), and BCMA Chimeric Antigen Receptor (CAR) T cells (Note: BCMA antibody-drug conjugates are not excluded)
- •History of progressive multifocal leukoencephalopathy, neurodegenerative condition or Central Nervous System (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded
- •Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
- •Cardiac ejection fraction <40% by Echocardiogram (Echo) or Multigated Acquisition (MUGA) scan
- •Cohort Specific Exclusion Criteria:
- •Cohort 2: Dose expansion: Prior treatment with a BCMA-directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment Cohort 3: Known malabsorption syndrome or pre-existing gastrointestinal (GI) condition that may impair absorption of lenalidomide; delivery of lenalidomide via nasogastric tube or gastrostomy tube is not allowed Cohort 4: Peripheral neuropathy grade ≥2 Cohort 5: Known malabsorption syndrome or pre-existing GI conditions that may impair absorption of pomalidomide; delivery of pomalidomide via nasogastric tube or gastrostomy tube is not allowed
- •Prior treatment with anti-Lymphocyte Activation Gene 3 (LAG-3) agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Programmed cell Death Protein 1 (PD-1) antibodies is permitted, as described in the protocol
- •Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol
- •Prior solid organ transplant
- •History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies
- •Prior treatment with anti-PD-1 or anti-PD-L1 agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) antibodies is permitted, as described in the protocol
- •Encephalitis or meningitis in the year prior to enrollment
- •History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment
- •Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
- •Prior solid organ transplant
- •History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies
- •Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol
- •Use of concomitant medications that are known to prolong the QT/QTcF interval including Class Ia and Class III antiarrhythmics at the time of informed consent
- •Ongoing use or anticipated use of food or drugs that are known strong/moderate cytochrome P450 (CYP)3A4 inhibitors, or strong CYP3A inducers within 14 days prior to first dose of nirogacestat
- •Known malabsorption syndrome or existing gastrointestinal GI condition that may impair absorption of nirogacestat; delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed
- •Known or suspected active Epstein-Barr Virus (EBV) infection
- •Known history of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)
- •Prior treatment with cevostamab or another agent with the same target [Fragment crystallizable Receptor-like 5 (FcRH5)]
- •Dose finding portion: Prior treatment with any BCMA-directed immunotherapy will not be exclusionary, as described in the protocol Dose expansion portion: Prior treatment with any T cell-engaging bispecific antibody directed against BCMA will be exclusionary, as described in the protocol
- •NOTE: Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Cohort 2: Linvolseltamab + Carfilzomib
Experimental
Linvoseltamab + Carfilzomib
干预措施: Carfilzomib (Drug)
Cohort 3: Linvoseltamab + Lenalidomide
Experimental
Linvoseltamab + Lenalidomide
干预措施: Linvoseltamab (Drug)
Cohort 1: Linvoseltamab + Daratumumab
Experimental
Linvoseltamab + Daratumumab
干预措施: Daratumumab (Drug)
Cohort 2: Linvolseltamab + Carfilzomib
Experimental
Linvoseltamab + Carfilzomib
干预措施: Linvoseltamab (Drug)
Cohort 1: Linvoseltamab + Daratumumab
Experimental
Linvoseltamab + Daratumumab
干预措施: Linvoseltamab (Drug)
Cohort 3: Linvoseltamab + Lenalidomide
Experimental
Linvoseltamab + Lenalidomide
干预措施: Lenalidomide (Drug)
Cohort 5: Linvoseltamab + Pomalidomide
Experimental
Linvoseltamab + Pomalidomide
干预措施: Linvoseltamab (Drug)
Cohort 4: Linvoseltamab + Bortezomib
Experimental
Linvoseltamab + Bortezomib
干预措施: Linvoseltamab (Drug)
Cohort 4: Linvoseltamab + Bortezomib
Experimental
Linvoseltamab + Bortezomib
干预措施: Bortezomib (Drug)
Cohort 5: Linvoseltamab + Pomalidomide
Experimental
Linvoseltamab + Pomalidomide
干预措施: Pomalidomide (Drug)
Cohort 6: Linvoseltamab + Isatuximab
Experimental
Linvoseltamab + Isatuximab
干预措施: Linvoseltamab (Drug)
Cohort 6: Linvoseltamab + Isatuximab
Experimental
Linvoseltamab + Isatuximab
干预措施: Isatuximab (Drug)
Cohort 7: Linvoseltamab + Fianlimab
Experimental
Linvoseltamab + Fianlimab
干预措施: Linvoseltamab (Drug)
Cohort 7: Linvoseltamab + Fianlimab
Experimental
Linvoseltamab + Fianlimab
干预措施: Fianlimab (Drug)
Cohort 8: Linvoseltamab + Cemiplimab
Experimental
Linvoseltamab + Cemiplimab
干预措施: Linvoseltamab (Drug)
Cohort 8: Linvoseltamab + Cemiplimab
Experimental
Linvoseltamab + Cemiplimab
干预措施: Cemiplimab (Drug)
Cohort 9: Linvoseltamab + Nirogacestat
Experimental
Linvoseltamab + Nirogacestat
干预措施: Linvoseltamab (Drug)
Cohort 9: Linvoseltamab + Nirogacestat
Experimental
Linvoseltamab + Nirogacestat
干预措施: Nirogacestat (Drug)
Cohort 10: Linvoseltamab + Cevostamab
Experimental
Linvoseltamab + Cevostamab
干预措施: Linvoseltamab (Drug)
Cohort 10: Linvoseltamab + Cevostamab
Experimental
Linvoseltamab + Cevostamab
干预措施: Cevostamab (Drug)
结局指标
主要结局
Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
时间窗: Up to 28 Days
Dose finding portion only
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 5 Years
Severity of TEAEs
时间窗: Up to 5 Years
Incidence of serious adverse events (SAEs)
时间窗: Up to 5 Years
Severity of SAEs
时间窗: Up to 5 Years
Incidence of adverse events of special interest (AESIs)
时间窗: Up to 5 Years
Severity of AESIs
时间窗: Up to 5 Years
Incidence of laboratory abnormalities
时间窗: Up to 5 Years
≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\]
Incidence of Serious Adverse Events (SAEs)
时间窗: Up to 5 Years
Incidence of Adverse Events of Special Interest (AESIs)
时间窗: Up to 5 Years
Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period
时间窗: Up to 28 Days
Dose finding portion only
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to 5 Years
次要结局
- Concentrations of total linvoseltamab in serum over time(Up to 5 Years)
- Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab(Up to 5 Years)
- Overall Survival (OS)(Up to 5 Years)
- Objective response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria(Up to 5 Years)
- Duration of response (DOR) by IMWG criteria(Up to 5 Years)
- Progression-free survival (PFS) as measured by IMWG criteria(Up to 5 Years)
- Rate of minimal residual disease (MRD) negative status by IMWG criteria(Up to 5 Years)
- Overall Response Rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria(Up to 5 Years)
- Duration of Response (DOR) by IMWG criteria(Up to 5 Years)
- Progression-Free Survival (PFS) as measured by IMWG criteria(Up to 5 Years)
- Rate of Minimal Residual Disease (MRD) negative status by IMWG criteria(Up to 5 Years)
- Incidence over time of Anti-Drug Antibodies (ADAs) to linvoseltamab(Up to 5 Years)
研究者
研究点 (82)
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