A Phase 1 Study to Assess Safety and Tolerability of REGN5837, an Anti-CD22 x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination With Odronextamab, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients With Aggressive B-Cell Non-Hodgkin Lymphomas (ATHENA-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 107
- 试验地点
- 38
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab
研究概览
简要总结
This study is researching an experimental drug called REGN5837 in combination with another drug, odronextamab (called "study drug[s]"), in patients with relapsed or refractory aggressive B-cell Non-Hodgkin Lymphomas (B-NHLs).
The study has 2 parts. The aim of the first part (dose escalation) is to find a safe dose of REGN5837 when given in combination with odronextamab.
The goal of the second part (dose expansion) is to use the REGN5837 drug dose found in the first part to see how well REGN5837 in combination with odronextamab works.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drugs
- How much study drug is in the blood at different times
- Whether the body makes 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
- 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
- •Have documented CD20+ aggressive B-NHL, with disease that has progressed after at least 2 lines of systemic therapy containing an anti-CD20 antibody and an alkylating agent, as described in the protocol.
- •Measurable disease on cross sectional imaging as defined in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate bone marrow, renal and hepatic function as defined in the protocol
- •Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed
- •During dose expansion phase of the study, participant should be willing to undergo mandatory tumor biopsies, if in the opinion of the investigator, the participant has an accessible lesion that can be biopsied without significant risk to the participant.
排除标准
- •Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab
- •Diagnosis of Mantle Cell Lymphoma (MCL)
- •Primary Central Nervous System (CNS) lymphoma or known involvement by non-primary CNS lymphoma, as described in the protocol
- •Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 14 days prior to first administration of study drug, whichever is shorter, as described in the protocol
- •Standard radiotherapy within 14 days of first administration of study drug, as described in the protocol
- •Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab
- •Co-morbid conditions, as described in the protocol
- •Infections, as described in the protocol
- •Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicase
- •NOTE: Other protocol defined inclusion / exclusion criteria apply
研究组 & 干预措施
Dose escalation portion
干预措施: Odronextamab (Drug)
Dose escalation portion
干预措施: REGN5837 (Drug)
Dose expansion portion
干预措施: REGN5837 (Drug)
Dose expansion portion
干预措施: Odronextamab (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab
时间窗: From Cycle 2, Day 15 to Cycle 4, Day 7 (each induction cycle is 21 days)
A DLT is defined as any non-haematologic and haematologic toxicity, as defined in the protocol, unless the event is clearly attributable to the underlying disease or to an extraneous cause (including concomitant medications).
Incidence of treatment-emergent adverse events (TEAEs) of REGN5837 in combination with odronextamab
时间窗: Up to approximatively 5 years
Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period.
Severity of TEAEs of REGN5837 in combination with odronextamab
时间窗: Up to approximatively 5 years
Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period.
Incidence of adverse events of special interest (AESIs) of REGN5837 in combination with odronextamab
时间窗: Up to approximatively 5 years
An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
Severity of AESIs of REGN5837 in combination with odronextamab
时间窗: Up to approximatively 5 years
An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab
时间窗: From Cycle 2, Day 1 to Cycle 2, Day 21 (each induction cycle is 21 days)
A DLT is defined as any non-haematologic and haematologic toxicity, as defined in the protocol, unless the event is clearly attributable to the underlying disease or to an extraneous cause (including concomitant medications).
Incidence of Treatment-Emergent Adverse Events (TEAEs) of REGN5837 in combination with odronextamab
时间窗: Up to approximatively 5 years
Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period.
Incidence of Adverse Events of Special Interest (AESIs) of REGN5837 in combination with odronextamab
时间窗: Up to approximatively 5 years
An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
次要结局
- Progression Free Survival (PFS) according to the Lugano Classification of response(Up to approximatively 5 years)
- Concentrations of REGN5837 in the serum(Up to 90 days post last study drug administration)
- Concentrations of odronextamab in the serum(Up to 90 days post last study drug administration)
- Incidence of anti-drug antibodies (ADAs) to REGN5837 over the study duration(Up to 90 days post last study drug administration)
- Incidence of ADAs to odronextamab over the study duration(Up to 90 days post last study drug administration)
- Titer of ADAs to REGN5837 over the study duration(Up to 90 days post last study drug administration)
- Titer of ADAs to odronextamab over the study duration(Up to 90 days post last study drug administration)
- Overall response rate (ORR) according to the Lugano Classification of response(Up to approximatively 5 years)
- Complete response (CR) rate according to the Lugano Classification of response(Up to approximatively 5 years)
- Progression free survival (PFS) according to the Lugano Classification of response(Up to approximatively 5 years)
- Overall survival (OS)(Up to approximatively 5 years)
- Duration of Response (DoR) according to the Lugano Classification of response(Up to approximatively 5 years)
- Occurrence of Anti-Drug Antibodies (ADAs) to REGN5837(Up to 90 days post last study drug administration)
- Occurrence of ADAs to odronextamab(Up to 90 days post last study drug administration)
- Magnitude of ADAs to REGN5837(Up to 90 days post last study drug administration)
- Magnitude of ADAs to odronextamab(Up to 90 days post last study drug administration)
- Objective Response Rate (ORR) according to the Lugano Classification of response(Up to approximatively 5 years)
- Complete Response (CR) according to the Lugano Classification of response(Up to approximatively 5 years)
- Overall Survival (OS)(Up to approximatively 5 years)