A Phase 3, Open label, Randomized Study Comparing the Efficacy and Safety of Odronextamab (REGN1979), an anti-CD20 × anti-CD3 bispecific antibody, in Combination with CHOP (Odro-CHOP) versus Rituximab in Combination with CHOP (R-CHOP) in Previously Untreated Participants with Diffuse Large B-cell Lymphoma (DLBCL) (OLYMPIA-3)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 419
- 试验地点
- 98
- 主要终点
- Part 1: Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
Study Objectives- Part 1 (Safety Run-in): To assess the safety, tolerability and dose limiting toxicities (DLTs) of odronextamab in combination with CHOP (Odro-CHOP) in participants previously untreated for Diffuse Large B-Cell Lymphoma (DLBCL) with high-risk features or participants with relapsed or refractory DLBCL (Part 1A), and to determine the dose of odronextamab to combine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in Part 2.
Study Objectives – Part 2: To compare the efficacy of Odro-CHOP with that of rituximab-CHOP (R-CHOP) in participants with previously untreated DLBCL with an (International Prognostic Index) IPI score ≥3, and subsequently in all participants with an IPI score ≥2.
研究设计
- 分配方式
- Randomized
- 主要目的
- Part 2: Randomised Portion
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol or R/R DLBCL for whom next available standard of care therapy is not available or deemed ineligible according to investigator (Part 1A only)
- •Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- •Life expectancy ≥ 12 months
- •International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only
- •Adequate hematologic and organ function, as defined in the protocol
- •Note: Other protocol-defined Inclusion criteria apply
排除标准
- •Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology
- •Another active malignancy, significant active disease or medical condition, as described in the protocol
- •Peripheral neuropathy Grade ≥3
- •Treatment with any systemic anti-lymphoma therapy , except for participants with R/R DLBCL and participants with DLBCL transformed from an indolent follicular lymphoma after treatment with systemic anti-lymphoma therapy.
- •Any other therapy or investigational treatment within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment
- •Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol
- •Allergy/hypersensitivity to study drugs, as described in the protocol
- •Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol.
- •Note: Other protocol-defined Exclusion criteria apply
结局指标
主要结局
Part 1: Incidence of dose limiting toxicities (DLTs)
Part 1: Incidence of dose limiting toxicities (DLTs)
Part 1: Incidence of treatment emergent adverse events (TEAEs)
Part 1: Incidence of treatment emergent adverse events (TEAEs)
Part 1: Severity of TEAEs
Part 1: Severity of TEAEs
Part 2: Progression free survival (PFS), assessed by independent central review (ICR)
Part 2: Progression free survival (PFS), assessed by independent central review (ICR)
次要结局
- Part 1 & 2: Best Overall response (BOR) as assessed by local investigators
- Part 1 & 2: CR as assessed by local investigators
- Part 1 & 2: Duration of response (DOR) as assessed by local investigators
- Part 1 & 2: Odronextamab concentrations in serum when administered with CHOP
- Part 1 & 2: Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration
- Part 1 & 2: Titer of ADA to odronextamab over the study duration
- Part 1 & 2: Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration
- Part 2: Event-free survival (EFS) assessed by ICR
- Part 2: Complete response (CR) assessed by ICR
- Part 2: Overall survival (OS)
- Part 2: PFS assessed by local investigator review
- Part 2: EFS assessed by local investigator review
- Part 2: BOR assessed by ICR
- Part 2: DOR assessed by ICR
- Part 2: Incidence of TEAEs
- Part 2: Severity of TEAEs
- Part 2: Measurable Residual Disease (MRD) status
- Part 2: Duration of MRD-negativity
- Part 2: Change in physical functioning as measured by EORTC QLQ C30
- Part 2: Change in patient reported outcomes, as measured by EORTC QLQ-C30
- Part 2: Change in patient reported outcomes, as measured by FACT-LymS
- Part 2: Change in patient reported outcomes, as measured by PGIS
- Part 2: Change in patient reported outcomes, as measured by PGIC
- Part 2: Change in patient reported outcomes, as measured by EQ-5D-5L
- Part 2: Change in score of the FACT-G GP5 item
研究者
Head EU Regulatory Affairs
Scientific
Regeneron Pharmaceuticals Inc.