A FIRST-IN-HUMAN (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
- 发起方
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Phase 1: Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab
研究概览
简要总结
Phase 1: Dose Escalation • To evaluate the safety, tolerability, and to determine RP2D regimens, of REGN17372 in combination with linvoseltamab in participants with RRMM
Phase 2: Dose Expansion • To assess the preliminary anti-tumor activity of the two RP2D regimens of REGN17372 in combination with linvoseltamab and of linvoseltamab monotherapy in participants with RRMM
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 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
Dexamethasone 3.3 mg/ml solution for injection/infusion
干预措施: Dexamethasone 3.3 mg/ml solution for injection/infusion (Drug)
Diphenhydramin-Hevert Injektionslösung, Diphenhydramine Hydrochloride Tablets 25 mg
干预措施: Diphenhydramin-Hevert Injektionslösung (Drug)
Diphenhydramin-Hevert Injektionslösung, Diphenhydramine Hydrochloride Tablets 25 mg
干预措施: Diphenhydramine Hydrochloride Tablets 25 mg (Drug)
Paracetamol 1000mg Tablets
干预措施: Paracetamol 1000mg Tablets (Drug)
REGN17372
干预措施: REGN17372 (Drug)
LYNOZYFIC 200 mg concentrate for solution for infusion, LYNOZYFIC 5 mg concentrate for solution for infusion
干预措施: LYNOZYFIC 200 mg concentrate for solution for infusion (Drug)
LYNOZYFIC 200 mg concentrate for solution for infusion, LYNOZYFIC 5 mg concentrate for solution for infusion
干预措施: LYNOZYFIC 5 mg concentrate for solution for infusion (Drug)
结局指标
主要结局
Phase 1: Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab
Phase 1: Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab
Phase 1: Occurrence of Treatment Emergent Adverse Events (TEAEs) associated with REGN17372 in combination with linvoseltamab
Phase 1: Occurrence of Treatment Emergent Adverse Events (TEAEs) associated with REGN17372 in combination with linvoseltamab
Phase 1: Severity of TEAEs associated with REGN17372 in combination with linvoseltamab
Phase 1: Severity of TEAEs associated with REGN17372 in combination with linvoseltamab
Phase 2: 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
Phase 2: 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
Phase 2: VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy
Phase 2: VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy
Phase 2: Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination study drugs
Phase 2: Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination study drugs
Phase 2: PR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy
Phase 2: PR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy
次要结局
- Phase 1 and Phase 2: Overall Survival (OS)
- Phase 2: Change from baseline in EORTC QLQ-C30 Role Functioning (RF)
- Phase 2: Change from baseline in EORTC QLQ-C30 pain
- Phase 2: Change from baseline in EORTC QLQ-C30 fatigue
- Phase 1 and Phase 2: Incidence of ADA to linvoseltamab
- Phase 1 and Phase 2: Magnitude of ADA to linvoseltamab
- Phase 1 and Phase 2: Concentrations of REGN17372 in serum
- Phase 1 and Phase 2: Concentrations of linvoseltamab in serum
- Phase 1 and Phase 2: Occurrence of Anti-Drug Antibodies (ADA) to REGN17372
- Phase 1 and Phase 2: Magnitude of ADA to REGN17372
- Phase 1 and Phase 2: Objective Response Rate (ORR) as assessed by IMWG response criteria as determined by the investigator
- Phase 1 and Phase 2: Complete response (CR) as assessed by IMWG response criteria as determined by the investigator
- Phase 1 and Phase 2: VGPR as assessed by IMWG response criteria, as determined by the investigator
- Phase 1 and Phase 2: Duration of Response (DOR) as assessed by IMWG criteria as determined by the investigator
- Phase 1 and Phase 2: Progression Free Survival (PFS) as assessed by IMWG criteria as determined by the investigator
- Phase 1 and Phase 2: Minimal Residual Disease (MRD) negative status (at 10^-5) in participants in CR or better
- Phase 1: ORR as assessed using the IMWG response criteria as determined by the investigator in patients receiving combination study drugs
- Phase 1:VGPR assessed using IMWG criteria as determined by the investigator in patients receiving combination study drugs
- Phase 2: Incidence of TEAEs
- Phase 2: Severity of TEAEs
- Phase 2: 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)
- Phase 2: Change from baseline in EORTC QLQ-C30 Physical Functioning (PF)
- Phase 2: Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL
- Phase 2: Time to definitive deterioration in EORTC QLQ-C30 PF
- Phase 2: Time to definitive deterioration in EORTC QLQ-C30 RF
- Phase 2: Time to definitive deterioration in EORTC QLQ-C30 pain
- Phase 2: Time to definitive deterioration in EORTC QLQ-C30 fatigue
- Phase 2: Time to first improvement in EORTC QLQ-C30 GHS/QoL
- Phase 2: Time to first improvement in EORTC QLQ-C30 PF
- Phase 2: Time to first improvement in EORTC QLQ-C30 RF
- Phase 2: Time to first improvement in EORTC QLQ-C30 pain
- Phase 2: Time to first improvement in EORTC QLQ-C30 fatigue
- Phase 2: Change from baseline in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS)
- Phase 2: Time to definitive deterioration in EORTC QLQ-MY20 DS
- Phase 2: Time to first improvement in EORTC QLQ-MY20 DS
- Phase 2: Change from baseline in EORTC QLQ-MY20 Treatment Side Effects (TSE)
- Phase 2: Time to definitive deterioration in EORTC QLQ-MY20 TSE
- Phase 2: Time to first improvement in EORTC QLQ-MY20 TSE
- Phase 2: Change from baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS)
- Phase 2: Time to definitive deterioration in EQ-5D-5L VAS
- Phase 2: Time to first improvement in EQ-5D-5L VAS
- Phase 2: Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT) Item GP5
- Phase 2: Patient-reported tolerability as measured by the Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE)
研究者
Medical Affairs
Scientific
Regeneron Pharmaceuticals Inc.