A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Genmab
- 入组人数
- 483
- 试验地点
- 324
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this trial is to find out if epcoritamab, also known as EPKINLY™ and GEN3013, is safe and works well as treatment for participants with DLBCL that are not responding to treatment, have grown in size, or have come back following treatment with at least 1 prior systemic cancer therapy. All participants in this trial will be randomly assigned to receive either epcoritamab or a pre-specified investigator's choice (standard of care) chemotherapy (either rituximab + gemcitabine + oxaliplatin [R-GemOx], or bendamustine + rituximab [BR]). Participants must have failed or be ineligible to receive an autologous stem cell transplant (ASCT).
Epcoritamab will be injected under the skin. Investigator's choice chemotherapy will be given intravenously.
Trial details include:
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The trial duration will be up to 5 years after last participant is randomized.
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All trial participants have a 21-day screening period, a treatment period, and a follow-up period that continues until death.
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The estimated trial duration for an individual participant depends upon the treatment arm assigned:
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Participants who receive epcoritamab will have 28-day treatment cycles. Epcoritamab will be given once weekly for the first 3 months, then every other week for 6 months, then every 28 days until lymphoma progression or unacceptable adverse events.
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Participants who receive investigator's choice (standard of care) chemotherapy will receive treatments either:
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R-GemOx: On Day 1 (or Day 1 & Day 2), and Day 15 (or Day 15 & Day 16) every 28 days, for up to 4 months; or
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BR: On Day 1 and Day 2 every 3 weeks for up to 4.5 months.
详细描述
The trial is an open label, multi-center, global phase-3 randomized trial of epcoritamab. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in participants with relapsed, refractory DLBCL who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.
Overall Survival (OS) is the primary endpoint in USA and in China, with the analysis population including all randomized participants. OS/Progression Free Survival (PFS) are dual-primary endpoints for rest of the world (outside US and China), with the analysis population also including all participants randomized.
The China sub-study of GCT3013-05 is registered under NCT07226752.
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
- •Main Inclusion Criteria:
- •Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 monoclonal antibody (mAb)-containing combination chemotherapy since lymphoma diagnosis
- •One of the confirmed histologies below with CD20-positivity:
- •DLBCL, not otherwise specified (NOS), including de novo or histologically transformed from follicular lymphoma (FL)
- •"Double-hit" or "triple-hit" DLBCL (technically classified in World Health Organization (WHO) 2016 as high-grade B-cell lymphoma (HGBCL), with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL
- •FL Grade 3B
- •T-cell/histiocyte-rich large B-cell lymphoma
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2
- •Failed previous HDT-ASCT or not eligible for high-dose therapy autologous stem cell transplant (HDT-ASCT) at screening
- •Participants must have detectable disease by positron emission tomography (PET) scan and measurable by computed tomography (CT) scan or magnetic resonance imaging (MRI)
- •Acceptable renal and liver function
- •Life expectancy >2 months on standard of care treatment
排除标准
- •Primary Central Nervous System (CNS) tumor or known CNS involvement
- •Any prior therapy with a bispecific antibody targeting CD3 and CD20
- •Major surgery within 4 weeks prior to randomization
- •Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
- •Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
- •Autologous stem cell transplant (ASCT) within 100 days of randomization
- •Treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 100 days prior to randomization
- •Seizure disorder requiring anti-epileptic therapy
- •Clinically significant cardiac disease
研究组 & 干预措施
Epcoritamab (GEN3013; DuoBody®CD3xCD20)
Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met
干预措施: Epcoritamab (Biological)
Investigator's choice of chemotherapy
R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met
BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met
干预措施: Investigator's Choice Chemotherapy (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 5 years
Overall Survival (OS)
时间窗: Up to approximately 5 years
次要结局
- Progression Free Survival (PFS)(Up to approximately 5 years)
- Overall Response Rate (ORR)(Up to approximately 5 years)
- Complete Response (CR) Rate(Up to approximately 5 years)
- Duration of Response (DOR)(Up to approximately 5 years)
- Time to Response (TTR)(Up to approximately 5 years)
- Duration of Minimal Residual Disease (MRD) Negative Status(Up to approximately 5 years)
- Rate of MRD Negative Status(Up to approximately 5 years)
- Time to Next Anti-lymphoma Therapy (TTNT)(Up to approximately 5 years)
- Number of Participants with Adverse Events (AEs)(Up to approximately 5 years)
- Number of Participants with Dose Interruptions and Delays(Up to approximately 5 years)
- Number of Participants with an Anti-epcoritamab Antibody Response(Up to approximately 5 years)
- Changes from Baseline in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)(Baseline up to approximately 5 years)
- Duration of Minimal Residual Disease (MRD) Negative Status(Up to approximately 5 years)
- Rate of MRD Negative Status(Up to approximately 5 years)
- Time to Next Anti-lymphoma Therapy (TTNT)(Up to approximately 5 years)
- Number of Participants with Adverse Events (AEs)(Up to approximately 5 years)
- Number of Participants with Dose Interruptions and Delays(Up to approximately 5 years)
- Number of Participants with an Anti-epcoritamab Antibody Response(Up to approximately 5 years)
- Changes from Baseline in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)(Baseline up to approximately 5 years)
- Progression Free Survival (PFS)(Up to approximately 5 years)
- Overall Response Rate (ORR)(Up to approximately 5 years)
- Complete Response (CR) Rate(Up to approximately 5 years)
- Duration of Response (DOR)(Up to approximately 5 years)
- Time to Response (TTR)(Up to approximately 5 years)