Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3×CD20) in Japanese Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A Phase 1/2, Open-Label, Dose-Escalation Trial With Expansion Cohorts
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Genmab
- 入组人数
- 78
- 试验地点
- 28
- 主要终点
- Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) in Japanese participants with relapsed, progressive or refractory B-cell lymphomas and Japanese participants with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior standard of care (SOC). The trial consists of two parts: Part 1, dose escalation (phase 1), and Part 2, expansion (phase 2).
The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase-2 dose (RP2D), as well as to establish the safety profile of epcoritamab in Japanese participants with relapsed, progressive or refractory B-cell lymphoma and Japanese participants with B-cell lymphomas that have achieved PR or CR.
In the expansion part, additional participants will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.
Part 2 of the trial will be initiated once the RP2D has been determined in Part 1. In Part 2, epcoritamab is investigated as a monotherapy and in combination with other SOC agents.
详细描述
All participants in the trial will receive epcoritamab, as monotherapy or in combination with SOC. The following regimens will be investigated in Part 2:
Arm 1: epcoritamab monotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)
Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with R/R FL
Arm 3: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated DLBCL with high risk features
Arm 4: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL who either failed prior autologous hematopoietic stem cell transplantation (ASCT), or are ineligible for autologous HSCT.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Must be at least 20 years of age, inclusive
- •Japanese participants
- •CD20 positivity at representative tumor biopsy
- •Diffuse large B-cell lymphoma (de novo or histologically transformed)
- •High-grade B-cell lymphoma
- •Primary mediastinal large B-cell lymphoma
- •Follicular lymphoma
- •Marginal zone lymphoma (nodal, extranodal of mucosa-associated lymphoid tissue, or splenic)
- •Small lymphocytic lymphoma
- •Diffuse large B-cell lymphoma (de novo or histologically transformed)
- •Follicular lymphoma grade 1-3A
- •Relapsed or refractory disease and previously treated with at least 2 lines of systemic antineoplastic therapy including at least 1 anti-CD20 monoclonal antibody (mAb)-containing therapy.
- •Measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)-CT scan
- •R/R FL grade 1, 2 or 3a, stage II, III, or IV, without evidence of transformation.
- •Previously treated with at least 1 prior anti-neoplastic agent, including anti-CD20 antibody
- •Must have a need for treatment initiation based on symptoms and/or disease burden (Groupe d'Etude des Lymphomes Folliculaires [GELF] criteria)
- •Eligible to receive R2 per investigator determination
- •One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) :
- •o DLBCL, not otherwise specified (NOS)
- •"Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B.
- •T-cell/histiocyte rich large B-cell lymphoma (LBCL)
- •International Prognostic Index (IPI) score ≥3
- •No prior therapy for DLBCL or FL grade 3B (G3B) other than nodal biopsy, corticosteroids, or palliative radiotherapy.
- •Eligible to receive R-CHOP per investigator determination
- •One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) including:
- •o DLBCL, NOS.
- •o "Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B.
- •T-cell/histiocyte rich LBCL
- •Relapsed or refractory to at least one prior therapy including at least one prior anti-CD20 antibody.
- •Either failed prior autologous hematopoietic stem cell transplantation (ASCT), or ineligible for autologous hematopoietic stem-cell transplantation (HSCT)
- •Eligible to receive GemOx per investigator determination
- •History of histologically confirmed CD20+ FL Grade 1-3a without evidence of transformation.
- •In CR or PR per Lugano criteria following first-line or second-line treatment with SOC regimen, including anti-CD20 antibody, and last dose of SOC within 6 months prior to enrollment
排除标准
- •Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening
- •Participants not eligible for high dose therapy with autologous hematopoietic stem cell transplantation due to personal choice, social issues, or similar
- •Known clinically significant cardiac disease
- •Chronic ongoing infectious diseases requiring treatment (excluding prophylactic treatment)
- •Exclusion criteria for Part 2, Arms 2 through 5:
- •FL Grade 3b
- •Histologic evidence of transformation to an aggressive lymphoma
- •Contraindication to rituximab or lenalidomide
- •Unwilling or unable to take aspirin prophylaxis or prophylactic anticoagulant as clinically indicated
- •Contraindication to any of the individual drugs of the R-CHOP regimen
- •Contraindication to any of the individual drugs of the GemOx regimen
- •FL Grade 3b
- •Histologic evidence of transformation to an aggressive lymphoma
研究组 & 干预措施
Arm 2: Epcoritamab + Rituximab + Lenalidomide
In participants with R/R FL
干预措施: Epcoritamab (Biological)
Arm 2: Epcoritamab + Rituximab + Lenalidomide
In participants with R/R FL
干预措施: Rituximab and lenalidomide (Drug)
Arm 1: Epcoritamab
In participants with DLBCL/FL.
干预措施: Epcoritamab (monotherapy) (Biological)
Arm 3: Epcoritamab + Rituximab + Cyclophosphamide+ Doxorubicin+ Vincristine + Prednisone
In participants with previously untreated DLBCL
干预措施: Epcoritamab (Biological)
Arm 3: Epcoritamab + Rituximab + Cyclophosphamide+ Doxorubicin+ Vincristine + Prednisone
In participants with previously untreated DLBCL
干预措施: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (Drug)
Arm 4: Epcoritamab + Gemcitabine + Oxaliplatin
In participants with relapsed/refractory DLBCL
干预措施: Epcoritamab (Biological)
Arm 5: Epcoritamab Maintenance
In participants with FL in CR or in PR following 1L or 2L SOC treatment
干预措施: Epcoritamab (maintenance) (Biological)
Arm 4: Epcoritamab + Gemcitabine + Oxaliplatin
In participants with relapsed/refractory DLBCL
干预措施: Gemcitabine and oxaliplatin (Drug)
结局指标
主要结局
Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: DLTs are assessed during the first cycle (28 days) in each cohort
Part 2, Arm 1: Objective Response Rate (ORR)
时间窗: Up to 1.5 years
Part 2, Arms 2-4: Number of Participants with DLTs
时间窗: DLTs are assessed during the first cycle (28 days) in arms 2-4
Part 2, Arms 2-5: Number of Participants with TEAEs
时间窗: From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years
次要结局
- Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: AUC from Time 0 to Infinity (AUCinf)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Maximum (Peak) Plasma Concentration (Cmax)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Time to Reach Cmax (Tmax)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Pre-dose (Trough) Concentrations (Cthrough)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Total Body Clearance of Drug from the Plasma (CL)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Volume of Distribution (Vd)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Elimination Half-life (t 1/2)(From first dose until treatment discontinuation, expected average of 1 year)
- Both parts: Number of Participants with Anti-Drug-Antibodies (ADAs)(From first dose until treatment discontinuation, expected average of 1 year)
- Part 2, Arm 1: Number of Participants with TEAEs(From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years)
- Part 1 and Part 2, Arms 2-5: ORR(Up to 1.5 years)
- Both parts: CR Rate(Up to 1.5 years)
- Both parts: Duration of Response (DOR)(Up to 1.5 years)
- Both parts: Progression Free Survival (PFS)(Up to 1.5 years)
- Part 2: Duration of CR (DoCR)(Up to 1.5 years)
- Part 2: Time to Response (TTR)(Up to 1.5 years)
- Part 1 and Part 2 arm 1: Time to Next Anti-lymphoma Therapy (TTNT)(Up to 1.5 years)
- Both parts: Overall Survival (OS)(Up to 1.5 years)