A Phase 3, Open Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Combination With Lenalidomide Versus Rituximab in Combination With Lenalidomide in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 580
- 试验地点
- 293
- 主要终点
- Severity of TEAEs for odronextamab in combination with lenalidomide
研究概览
简要总结
This study is researching an experimental drug called odronextamab (referred to as study drug), in combination with lenalidomide. The study is focused on participants who have one of two types of cancer: Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's Lymphoma (NHL).
This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled).
The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before.
The aim of Part 2, of the study is to assess how well the combination of the study drug and lenalidomide works compared to the combination of rituximab (called "the comparator drug") and lenalidomide. The combination of comparator drug and lenalidomide is the current standard-of-care treatment for relapsed/refractory FL and/or MZL. Standard-of-care means the usual medication expected and used when receiving treatment for a condition.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drug in combination with lenalidomide
- How much study drug is in the blood at different times
- Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
- The impact from the study drug on quality-of-life and ability to complete routine daily activities
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator, as described in the protocol.
- •Must have refractory disease or relapsed after at least 1 prior line (with a duration of at least 2 cycles) of systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-Cluster of Differentiation 20 (CD20) monoclonal antibody, and participant should meet indication for treatment, as described in the protocol.
- •Have measurable disease on cross sectional imaging documented by diagnostic Computed Tomography [CT], or Magnetic Resonance Imaging [MRI] imaging, as described in the protocol.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate hematologic and organ function, as described in the protocol.
- •All study participants must:
- •Have an understanding that lenalidomide could have a potential teratogenic risk.
- •Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide.
- •Agree not to share study medication with another person.
- •Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide.
排除标准
- •Primary Central Nervous System (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS NHL, as described in the protocol.
- •Participants with current or past histological evidence of high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL.
- •History of or current relevant CNS pathology, as described in the protocol.
- •A malignancy other than NHL (inclusion diagnosis) unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.
- •Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol.
- •Allergy/hypersensitivity to study drugs or excipients. as described in the protocol.
- •Active infection as defined in the protocol.
- •Note: Other protocol-defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Odronextamab+Lenalidomide
In part 1 (safety run-in), participants with R/R indolent lymphoma (FL and MZL), will receive odronextamab in combination with lenalidomide.
In part 2, 1:1 randomized participants with R/R FL and MZL, will receive odronextamab in combination with lenalidomide.
干预措施: Lenalidomide (Drug)
Odronextamab+Lenalidomide
In part 1 (safety run-in), participants with R/R indolent lymphoma (FL and MZL), will receive odronextamab in combination with lenalidomide.
In part 2, 1:1 randomized participants with R/R FL and MZL, will receive odronextamab in combination with lenalidomide.
干预措施: Odronextamab (Drug)
Rituximab+Lenalidomide
In part 2 only, 1:1 randomized participants with R/R FL and ML, will receive rituximab in combination with lenalidomide (R2) followed by lenalidomide monotherapy.
干预措施: Rituximab (Drug)
Rituximab+Lenalidomide
In part 2 only, 1:1 randomized participants with R/R FL and ML, will receive rituximab in combination with lenalidomide (R2) followed by lenalidomide monotherapy.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Severity of TEAEs for odronextamab in combination with lenalidomide
时间窗: Up to 2 years
Part 1
Progression-Free Survival (PFS) as assessed by Independent Central Review (ICR)
时间窗: Up to 5 years
Part 2
Incidence of Dose Limiting Toxicities (DLTs) for odronextamab in combination with lenalidomide
时间窗: Up to 35 days
Part 1
Incidence of Treatment Emergent Adverse Events (TEAEs) for odronextamab in combination with lenalidomide
时间窗: Up to 2 years
Part 1
Progression-Free Survival (PFS) as assessed by Independent Central Review (ICR) in participants with R/R FL and participants with indolent lymphoma
时间窗: Up to 5 years
Part 2
次要结局
- Odronextamab concentrations in serum(Up to 30 months)
- Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2(Up to 2 years)
- Overall change in patient reported outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)(Up to 5 years)
- BOR as assessed by ICR(Up to 30 months)
- DOR as assessed by ICR(Up to 5 years)
- Severity of TEAEs for odronextamab in combination with lenalidomide versus R2(Up to 2 years)
- PFS as assessed by investigator review(Up to 5 years)
- EFS as assessed by local investigator review(Up to 5 years)
- Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)(Up to 5 years)
- Overall change in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)(Up to 5 years)
- Incidence of Anti-Drug Antibodies (ADA) to odronextamab(Up to 30 months)
- Overall change in Patient Reported Outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)(Up to 5 years)
- Incidence of Anti-drug Antibodies (ADA) to odronextamab(Up to 30 months)
- Magnitude of ADAs to odronextamab(Up to 30 months)
- Best Overall Response (BOR) as assessed by investigator review(Up to 30 months)
- Duration of Response (DOR) as assessed by investigator review(Up to 5 years)
- Complete Response (CR) as assessed by ICR(Up to 30 months)
- Overall Survival (OS)(Up to 5 years)
- Event Free Survival (EFS) as assessed by ICR(Up to 5 years)
- Time To Next anti-lymphoma Treatment (TTNT)(Up to 5 years)
- Change from first assessment in Patient Global Impression on Severity (PGIS)(Up to 5 years)
- Change from first assessment in Patient Global Impression on Change (PGIC)(Up to 5 years)
- Change from first assessment in the Global Population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire(Up to 5 years)