A Phase 1 Study to Assess Safety and Tolerability of Odronextamab (REGN1979) an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, and Cemiplimab (REGN2810), an Anti-Programmed Death-1 Monoclonal Antibody in Patients With B-Cell Malignancies (CLIO-1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 30
- 主要终点
- Incidence of dose limiting toxicities (DLTs) of cemiplimab in combination with odronextamab
研究概览
简要总结
This study is researching a combination of 2 experimental drugs, referred to as "study drugs", called odronextamab (also known as REGN1979) and cemiplimab (also known as REGN2810). The study is focused on patients who have relapse/refractory aggressive B-cell lymphoma. The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose regimen for the combination with odronextamab.
This study is also looking at several other research questions, including:
- What side effects may happen from taking the study drugs
- How effective the study drugs are against the disease
- How much study drug is in the blood at different times
- Whether the body makes substances or protein called antibodies against the study drugs (that could make the drugs 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
- 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
- •Have documented CD20+ aggressive B-cell NHL that is either not responsive to or relapsed after at least 2 prior lines of systemic therapy, for whom treatment with an anti-CD20 antibody may be appropriate. In addition, prior treatments should at least contain an anti-CD20 antibody and an alkylating agent.
- •Must have at least 1 nodal lesion (≥1.5 cm), or at least one extranodal lesion with longest transverse diameter (LDi) greater than 1.0 cm, documented by diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]).
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Adequate bone marrow and hepatic function, as defined in the protocol
- •Willing and able to comply with clinic visits and study-related procedures
- •Provide signed informed consent
排除标准
- •Primary central nervous system (CNS) lymphoma, or known or suspected CNS involvement by non-primary CNS NHL
- •History of or current relevant CNS pathology, as described in the protocol
- •Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-mediated adverse events (iAEs)
- •Prior therapies, as described in the protocol
- •Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or other uncontrolled infection
- •Cytomegalovirus infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay until the infection is well controlled.
- •Known hypersensitivity to both allopurinol and rasburicase
- •Pregnant or breastfeeding women
- •Women of childbearing potential, or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose, as defined in the protocol
- •Patients prior diagnosis of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
- •Note: Other protocol-defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Dose escalation phase
Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose (RP2D) regimen(s) for the combination of odronextamab and cemiplimab.
干预措施: cemiplimab (Drug)
Dose expansion phase
RP2D administration of the combination treatment.
干预措施: cemiplimab (Drug)
Dose escalation phase
Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose (RP2D) regimen(s) for the combination of odronextamab and cemiplimab.
干预措施: odronextamab (Drug)
Dose expansion phase
RP2D administration of the combination treatment.
干预措施: odronextamab (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs) of cemiplimab in combination with odronextamab
时间窗: Up to 28 days
Incidence of treatment emergent adverse events (TEAEs) of cemiplimab in combination with odronextamab
时间窗: Up to 18 months
Incidence of adverse events of special interest (AESIs) of cemiplimab in combination with odronextamab
时间窗: Up to 18 months
Severity of AESIs of cemiplimab in combination with odronextamab
时间窗: Up to 18 months
Severity of TEAEs of cemiplimab in combination with odronextamab
时间窗: Up to 18 months
次要结局
- Odronextamab and cemiplimab concentrations in serum(Up to 18 months)
- Titer of ADAs to odronextamab and cemiplimab over time(Up to 18 months)
- Complete response (CR) rate as assessed by investigator(Up to 18 months)
- Incidence of anti-drug antibodies (ADAs) to odronextamab and cemiplimab over time(Up to 18 months)
- Duration of response as assessed by investigator(Up to 18 months)
- Incidence of neutralizing antibodies (Nabs) to odronextamab and cemiplimab over time(Up to 18 months)
- Titer of Nabs to odronextamab and cemiplimab over time(Up to 18 months)
- Overall response rate as assessed by investigator(Up to 18 months)