NCT06669247招募中1 期
A First-in-Human (FIH) Phase 1/2 Study to Assess Safety, Tolerability, and Preliminary Anti-Tumor Activity of REGN7945, an Anti-CD38 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
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
- 186
- 试验地点
- 16
- 主要终点
- Incidence of dose limiting toxicities (DLTs) from the first dose of REGN7945 in combination with linvoseltamab
研究概览
简要总结
This study is researching an experimental drug called REGN7945 in combination with another experimental drug called linvoseltamab, (also known as REGN5458) (each individually called a "study drug" or "study drugs" when combined).
This study is the first time REGN7945 will be tested in humans. Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after several other therapies had failed.
The aim of the study is to see how safe, tolerable, and effective REGN7945 is when given in combination with linvoseltamab, compared with linvoseltamab alone.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drug(s)
- How many people treated with REGN7945 and linvoseltamab compared to linvoseltamab alone have improvement of their multiple myeloma and by how much
- How long people benefit from receiving REGN7945 in combination with linvoseltamab compared with linvoseltamab alone
- How much study drug(s) is in the blood at different times
- Whether the body makes antibodies against the study drugs(s) (which could make the study drug(s) less effective or could lead to side effects)
- If there is any change in pain and cancer-related symptoms, how well people are able to function, and their quality of life when taking the study drug(s)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 as described in the protocol
- •Received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD), and 1 proteasome inhibitor (PI) and have demonstrated disease progression on or after the last therapy, as defined in the protocol. Prior treatment with other BCMA directed immunotherapies, including BCMA CAR-T cells and BCMA antibody-drug conjugates (Phase 1 and 2), and with BCMA x CD3 bispecific antibodies (Phase 1 only), is allowed
- •Participants must have the measurable disease for response assessment as described in the protocol
- •Adequate hematologic, hepatic, and renal function as described in the protocol
排除标准
- •Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis (including myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
- •History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment
- •Treatment with systemic corticosteroid treatment with more than 10 mg per day of prednisone or steroid equivalent within 72 hours of start of study drug
- •Participants who have known central nervous system (CNS) involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), history of a neurocognitive condition or CNS disorder, or history of seizure within 12 months prior to study enrollment
- •Live or live attenuated vaccination within 28 days before first study drug administration with a vector that has replicative potential
- •Has received a COVID-19 vaccination within 1 week of planned start of study medication as described in the protocol
- •Myelodysplastic syndrome or another malignancy in the past 3 years, except for nonmelanoma skin cancer, in situ carcinoma, thyroid cancer, or low-risk early stage prostate adenocarcinoma, as described in the protocol
- •Significant cardiovascular disease as described in the protocol
- •Uncontrolled infection with HIV, Hep B or Hep C infection, or other uncontrolled infection, such as CMV, as described in the protocol
- •Known hypersensitivity to both allopurinol and rasburicase
- •Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
REGN7945+Linvoseltamab
Experimental
Phase 1 Phase 2
干预措施: REGN7945+Linvoseltamab (Drug)
Linvoseltamab
Experimental
Phase 2
干预措施: REGN7945+Linvoseltamab (Drug)
Linvoseltamab
Experimental
Phase 2
干预措施: Linvoseltamab (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs) from the first dose of REGN7945 in combination with linvoseltamab
时间窗: Up to 21 days
Phase 1
Incidence of treatment emergent adverse events (TEAEs) during the treatment period with REGN7945 in combination with linvoseltamab
时间窗: Up to 5 years
Phase 1
Severity of TEAEs during the treatment period with REGN7945 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 therapy
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 therapy
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
- Concentrations of REGN7945 in the serum(Up to 5 years)
- Incidence of TEAEs(Up to 5 years)
- Severity of TEAEs(Up to 5 years)
- Concentrations of linvoseltamab in the serum(Up to 5 years)
- Titer of ADA to REGN7945(Up to 5 years)
- Incidence of anti-drug antibodies (ADA) to REGN7945(Up to 5 years)
- Incidence of ADA to linvoseltamab(Up to 5 years)
- Titer of ADA to linvoseltamab(Up to 5 years)
- Change 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 in EORTC QLQ-C30 Physical Functioning (PF)(Up to 5 years)
- Change in EORTC QLQ-C30 Role Functioning (RF)(Up to 5 years)
- Change in EORTC QLQ-C30 pain(Up to 5 years)
- Change 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 in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS)(Up to 5 years)
- Change in EORTC QLQ-MY20 Treatment Side Effects (TSE)(Up to 5 years)
- Change in EORTC QLQ-MY20 Body Image (BI)(UP to 5 years)
- Change in EORTC QLQ-MY20 Future Perspective (FP)(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-MY20 DS(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-MY20 TSE(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-MY20 BI(Up to 5 years)
- Time to definitive deterioration in EORTC QLQ-MY20 FP(Up to 5 years)
- Time to first improvement in EORTC QLQ-MY20 DS(Up to 5 years)
- Time to first improvement in EORTC QLQ-MY20 TSE(Up to 5 years)
- Time to first improvement in EORTC QLQ-MY20 BI(Up to 5 years)
- Time to first improvement in EORTC QLQ-MY20 FP(Up to 5 years)
- Change 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 days)
- Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT)-Item GP5(Up to 5 years)
- Objective Response Rate (ORR) as measured by IMWG criteria as determined by the investigator(Up to 5 years)
- Complete response (CR) rate as measured by IMWG criteria as determined by the investigator(Up to 5 years)
- Duration of response (DOR) by IMWG criteria as determined by the investigator(Up to 5 years)
- Progression Free Survival (PFS) as measured by IMWG criteria as determined by the investigator(Up to 5 years)
- Achievement of 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)
研究者
研究点 (16)
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