A FIH Phase 1/2 Study to Assess Safety, Tolerability, and Preliminary Anti-Tumor Activity of REGN17372, an Anti-GPRC5D x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination With Linvoseltamab, an Anti-BCMA x Anti-CD3 Bispecific Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 8
- 主要终点
- Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab
研究概览
简要总结
This study is researching a drug called REGN17372 used with another drug called linvoseltamab (each individually called "study drug" or "study drugs" when combined) in participants with relapsed (when a tumor comes back) or refractory (when a tumor does not respond to treatment) multiple myeloma. This study is the first time REGN17372 will be given to humans.
The aim of the study is to understand if REGN17372 can be given safely with linvoseltamab, and if so, what dosing regimen should be used for this treatment combination, in comparison with linvoseltamab alone.
The study is looking at:
- What side effects may happen from taking REGN17372 with linvoseltamab
- How well REGN17372 and linvoseltamab, or linvoseltamab alone, work in treating multiple myeloma
- What is the best dose of REGN17372 when given with linvoseltamab
- How much study drug(s) are in the blood at different times
- Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)
- If and how REGN17372 and linvoseltamab affect the overall quality of life, daily activities, symptoms and treatment side effects based on participant own feedback (Phase 2)
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
- •Participants with RRMM who have exhausted (or are not a candidate for) all therapeutic options that are expected to provide meaningful clinical benefit and have received at least 3 lines of therapy as defined in the protocol
- •ECOG performance status score ≤1
- •Participants must have measurable disease for response assessment as described in the protocol
- •Adequate hematologic, cardiac, hepatic, and renal function, as described in the protocol
排除标准
- •Participants with non-secretory MM, active plasma cell leukemia, known amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome as defined in the protocol
- •Participants who have known MM brain lesions or CNS involvement
- •Participants with a history of PML, a neurocognitive condition or CNS movement disorder, or a history of seizure within 12 months prior to entering screening
- •Prior treatment with GPRC5D-directed immunotherapies (phase 1 and phase 2) and/or prior treatment with a BCMAxCD3 bispecific antibody (phase 2)
- •Note: Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
REGN17372 + Linvoseltamab
Phase 1 Phase 2
干预措施: REGN17372+Linvoseltamab (Drug)
Linvoseltamab monotherapy
Phase 2
干预措施: Linvoseltamab (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab
时间窗: Up to 35 days
Phase 1
Occurrence of Treatment Emergent Adverse Events (TEAEs) associated with REGN17372 in combination with linvoseltamab
时间窗: Up to 5 years
Phase 1
Severity of TEAEs associated with REGN17372 in combination with linvoseltamab
时间窗: Up to 5 years
Phase 1
Very Good Partial Response (VGPR) or better as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria in patients receiving combination study drugs
时间窗: Within 12 weeks of starting cycle 1
Phase 2
VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy
时间窗: Within 12 weeks of starting cycle 1
Phase 2
Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination study drugs
时间窗: Within 12 weeks of starting cycle 1
Phase 2
PR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy
时间窗: Within 12 weeks of starting cycle 1
Phase 2
次要结局
- Severity of TEAEs(Up to 5 years)
- Concentrations of REGN17372 in serum(Up to 5 years)
- Concentrations of linvoseltamab in serum(Up to 5 years)
- Occurrence of Anti-Drug Antibodies (ADA) to REGN17372(Up to 5 years)
- Magnitude of ADA to REGN17372(Up to 5 years)
- Incidence of ADA to linvoseltamab(Up to 5 years)
- Magnitude of ADA to linvoseltamab(Up to 5 years)
- Objective Response Rate (ORR) as assessed by IMWG response criteria as determined by the investigator(Up to 5 years)
- Complete response (CR) as assessed by IMWG response criteria as determined by the investigator(Up to 5 years)
- VGPR as assessed by IMWG response criteria, as determined by the investigator(Up to 5 years)
- Duration of Response (DOR) as assessed by IMWG criteria as determined by the investigator(Up to 5 years)
- Progression Free Survival (PFS) as assessed by IMWG criteria as determined by the investigator(Up to 5 years)
- Minimal Residual Disease (MRD) negative status (at 10^-5) in participants in CR or better(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- ORR as assessed using the IMWG response criteria as determined by the investigator in patients receiving combination study drugs(Within 12 weeks of starting cycle 1)
- VGPR assessed using IMWG criteria as determined by the investigator in patients receiving combination study drugs(Within 12 weeks of starting cycle 1)
- Incidence of TEAEs(Up to 5 years)
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Global Health Status / Quality of Life (GHS/QoL)(Up to 5 years)
- Change from baseline in EORTC QLQ-C30 Physical Functioning (PF)(Up to 5 years)
- Change from baseline in EORTC QLQ-C30 Role Functioning (RF)(Up to 5 years)
- Change from baseline in EORTC QLQ-C30 pain(Up to 5 years)
- Change from baseline in EORTC QLQ-C30 fatigue(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-C30 PF(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-C30 RF(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-C30 pain(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-C30 fatigue(Up to 5 years)
- Time to first improvement in EORTC QLQ-C30 GHS/QoL(Up to 5 years)
- Time to first improvement in EORTC QLQ-C30 PF(Up to 5 years)
- Time to first improvement in EORTC QLQ-C30 RF(Up to 5 years)
- Time to first improvement in EORTC QLQ-C30 pain(Up to 5 years)
- Time to first improvement in EORTC QLQ-C30 fatigue(Up to 5 years)
- Change from baseline in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS)(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-MY20 DS(Up to 5 years)
- Time to first improvement in EORTC QLQ-MY20 DS(Up to 5 years)
- Change from baseline in EORTC QLQ-MY20 Treatment Side Effects (TSE)(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-MY20 TSE(Up to 5 years)
- Time to first improvement in EORTC QLQ-MY20 TSE(Up to 5 years)
- Change from baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS)(Up to 5 years)
- Time to definitive deterioration in EQ-5D-5L VAS(Up to 5 years)
- Time to first improvement in EQ-5D-5L VAS(Up to 5 years)
- Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT) Item GP5(Up to 5 years)
- Patient-reported tolerability as measured by the Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 5 years)