NCT03761108招募中1 期
Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 387
- 试验地点
- 76
- 主要终点
- Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
研究概览
简要总结
The main purpose of this study is to learn about the safety of linvoseltamab and to find out what is the best dose of linvoseltamab to give to patients with multiple myeloma and to look for any signs that linvoseltamab can effectively treat cancer.
The study is looking at several other research questions, including:
- Side effects that may be experienced by people receiving linvoseltamab
- How linvoseltamab works in the body
- How much linvoseltamab is present in the blood
- How linvoseltamab may work to treat cancer
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 ≤ 1
- •Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
- •Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.
- •Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:
- •a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
- •Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:
- •a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD.
- •Phase 2 (Cohorts 1 and 2):
- •Patients with MM whose disease meets the following criteria:
- •a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
- •Phase 2 (Cohort 3):
- •Patients with MM whose disease meets the following criteria:
- •Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
- •Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
- •Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.
- •AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellular therapy then:
- •Treatment with a CAR-T must have been associated with a response of PR or better, and
- •If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with linvoseltamab.
排除标准
- •1. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Patients with known MM brain lesions or meningeal involvement
- •Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)
- •Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excluded and BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort
- •5. History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
- •Note: Other protocol defined inclusion / exclusion criteria apply
研究组 & 干预措施
Linvoseltamab - Phase 1
Experimental
Phase 1 has two parts. Part 1, consists of linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration.
干预措施: Linvoseltamab (Drug)
Linvoseltamab - Phase 2 - Cohort 1
Experimental
Low Dose of linvoseltamab IV monotherapy.
干预措施: Linvoseltamab (Drug)
Linvoseltamab - Phase 2 - Cohort 2
Experimental
High Dose of linvoseltamab IV monotherapy.
干预措施: Linvoseltamab (Drug)
Linvoseltamab - Phase 2 - Cohort 3
Experimental
Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV linvoseltamab monotherapy.
干预措施: Linvoseltamab (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
时间窗: Up to 28 days
Phase 1 and Phase 2 for Japanese cohort only
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: Up to 5 years
Phase 1
Incidence and severity of adverse events of special interest (AESI)
时间窗: Up to 5 years
Phase 1
Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
时间窗: Up to 5 years
Phase 2, cohorts 1 and 2
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
时间窗: Up to 28 days
Phase 1 and Phase 2 for Japanese cohort only
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: Up to 5 years
Phase 1 Note: Phase 1, part 2 is not applicable for US.
Incidence and severity of adverse events of special interest (AESI)
时间窗: Up to 5 years
Phase 1 Note: Phase 1, part 2 is not applicable for US.
Assessment of the pharmacokinetics (PK) of linvoseltamab
时间窗: Up to 5 years
Phase 1 part 2
Concentrations of linvoseltamab in serum over time
时间窗: Up to 5 years
Phase 2, for Japanese cohort only
Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
时间窗: Up to 5 years
Phase 2, cohorts 1 and 2
Incidence and severity of cytokine release syndrome (CRS) with linvoseltamab
时间窗: Up to 5 years
Phase 2, cohort 3
ORR of IV linvoseltamab as assessed by investigator
时间窗: Up to 5 years
Phase 2, cohort 3
次要结局
- Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria(Up to 5 years)
- DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria(Up to 5 years)
- Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria(Up to 5 years)
- PFS as determined by an investigator, measured using the IMWG criteria(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
- ORR as measured as determined by blinded IRC, as measured using the IMWG criteria(Up to 5 years)
- ORR as determined by the investigator, measured using the IMWG criteria(Up to 5 years)
- Change in patient-reported global health status/QoL per EORTC QLQ-C30(Baseline up to Up to 5 years)
- Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30(Up to 5 years)
- Concentrations of linvoseltamab in the serum over time(Up to 5 years)
- Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab(Up to 5 years)
- Titer of anti-drug antibodies (ADAs) to linvoseltamab over time(Up to 5 years)
- Incidence of neutralizing antibodies (NAb) to linvoseltamab over time(Up to 5 years)
- Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria(Up to 5 years)
- DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria(Up to 5 years)
- Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria(Up to 5 years)
- PFS as determined by an investigator, measured using the IMWG criteria(Up to 5 years)
- Rate of minimal residual disease (MRD) negative status, using the IMWG criteria(Up to 5 years)
- Rate of MRD negative status(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
- ORR as measured as determined by blinded IRC, as measured using the IMWG criteria(Up to 5 years)
- ORR as determined by the investigator, measured using the IMWG criteria(Up to 5 years)
- Effects of linvoseltamab on health-related quality of life (HRQoL) and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)(Up to 5 years)
- Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])(Up to 5 years)
- Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])(Up to 5 years)
- Change in patient-reported global health status/QoL per EORTC QLQ-C30(Baseline up to Up to 5 years)
- Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30(Up to 5 years)
- Effects of linvoseltamab on general health status per EQ-5D-3L(Up to 5 years)
- Effects of linvoseltamab on patient-reported functions and symptoms per EORTC QLQ-C30(Up to 5 years)
- Effects of linvoseltamab on patient-reported functions and symptoms per QLQ-MY20(Up to 5 years)
- Incidence and severity of TEAEs with linvoseltamab(Up to 5 years)
- Incidence and severity of AESIs with linvoseltamab(Up to 5 years)
研究者
研究点 (76)
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相关资讯
Belantamab Mafodotin Triplet Demonstrates Improved Overall Survival in Relapsed/Refractory Multiple Myeloma- The DREAMM-7 phase 3 trial showed that belantamab mafodotin, bortezomib, and dexamethasone (BVd) significantly improved overall survival in relapsed/refractory multiple myeloma patients.
- BVd demonstrated a 42% reduction in the risk of death compared to daratumumab, bortezomib, and dexamethasone (DVd), with a projected median OS of 84 months versus 51 months.
- The belantamab mafodotin combination also achieved statistically significant superiority in minimal residual disease (MRD) negativity compared to the daratumumab combination.
- Regulatory filings for belantamab mafodotin combinations have been accepted in multiple major markets, potentially establishing a new standard of care.last yearAggressive Supportive Care May Reduce Infection Risk Following Linvoseltamab Treatment in Multiple Myeloma- Aggressive supportive care is crucial following linvoseltamab and BCMA bispecific antibody treatments to prevent high-grade infections, especially in community settings.
- Intravenous immunoglobulin and infection prophylaxis are essential components of supportive care to mitigate the risk of severe infections post-immunotherapy.
- Reducing the dosing frequency of bispecific antibodies, as seen with teclistamab, may also decrease the risk of infections over time.
- Phase 1/2 LINKER-MM1 trial data highlights the efficacy of linvoseltamab but also underscores the importance of managing treatment-related infection incidence.2 years ago