A Phase 3, Open-Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20x Anti-CD3 Bispecific Antibody, Combined With Chemotherapy Versus Rituximab Combined With Chemotherapy in Previously Untreated Participants With Follicular Lymphoma (OLYMPIA-2)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 733
- 试验地点
- 250
- 主要终点
- Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy
研究概览
简要总结
This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma. Follicular lymphoma is a type of non-Hodgkin lymphoma or NHL. Participants with follicular lymphoma that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory") are eligible to take part only in Part 1A of the study.
This study is made up of 3 parts: Part 1A (non-randomized), Part 1B and Part 2 (randomized - controlled).
The aim of Part 1A and Part 1B of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy to be used in Part 2 of the study.
The aim of Part 2 of the study is to assess how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab and chemotherapy (the current standard-of-care for NHL). 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
- 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
- •Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV
- •For Part 1A: previously untreated participants who have Follicular Lymphoma International Prognostic Index (FLIPI)-1 score of 3 to 5, or R/R FL
- •For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5
- •For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5
- •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 0-2
- •Adequate bone marrow and hepatic function.
排除标准
- •Participants with central nervous system lymphoma or leptomeningeal lymphoma
- •Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
- •Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma
- •Recent major surgery and history or organ transplantation
- •A malignancy other than NHL unless the participant is adequately and definitively treated and 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.
- •Note: Other protocol-defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Rituximab + Chemotherapy
In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
干预措施: Cyclophosphamide (Drug)
Odronextamab + Chemotherapy
Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.
干预措施: Odronextamab (Drug)
Odronextamab + Chemotherapy
Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.
干预措施: Cyclophosphamide (Drug)
Odronextamab + Chemotherapy
Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.
干预措施: Doxorubicin (Drug)
Odronextamab + Chemotherapy
Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.
干预措施: Prednisone/Prenisolone (Drug)
Rituximab + Chemotherapy
In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
干预措施: Odronextamab (Drug)
Rituximab + Chemotherapy
In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
干预措施: Rituximab (Drug)
Rituximab + Chemotherapy
In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
干预措施: Doxorubicin (Drug)
Rituximab + Chemotherapy
In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
干预措施: Vincristine (Drug)
Rituximab + Chemotherapy
In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
干预措施: Prednisone/Prenisolone (Drug)
Odronextamab + Chemotherapy + Maintenance
In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy [CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)], followed by odronextamab monotherapy maintenance.
干预措施: Odronextamab (Drug)
Odronextamab + Chemotherapy + Maintenance
In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy [CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)], followed by odronextamab monotherapy maintenance.
干预措施: Vincristine (Drug)
Odronextamab + Chemotherapy + No maintenance
In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.
干预措施: Odronextamab (Drug)
Odronextamab + Chemotherapy + No maintenance
In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.
干预措施: Vincristine (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy
时间窗: Up to 35 days
Part 1, DLT period
Complete Response rate at 30 months (CR30) assessed by independent central review (ICR)
时间窗: Up to 30 months
Part 2
Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy
时间窗: Up to 2 years
Part 1, Treatment period
Severity of TEAEs of odronextamab in combination with chemotherapy
时间窗: Up to 2 years
Part 1, Treatment period
次要结局
- PFS as assessed by local investigator(Up to 5 years)
- Incidence of neutralizing antibodies (NAb) to odronextamab(Up to 30 months)
- Change in patient reported physical functioning scale scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30)(Up to 5 years)
- Best overall response (BOR) as assessed by the investigator(Up to 30 months)
- Progression free survival (PFS) as assessed by ICR(Up to 5 years)
- Change in patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30(Up to 5 years)
- Change in cancer disease as measured by EORTC-QLQ-C30(Up to 5 years)
- Incidence of anti-odronextamab antibodies (ADAs)(Up to 30 months)
- Overall Survival (OS)(Up to 5 years)
- Change in patient-reported treatment side effects burden per Functional Assessment of Cancer Therapy-General Global Population Item 5 (FACT-G GP5)(Up to 5 years)
- Titers of ADAs to odronextamab(Up to 30 months)
- CR30 as assessed by local investigator(Up to 30 months)
- BOR as assessed by local investigator(Up to 30 months)
- BOR as assessed by ICR(Up to 30 months)
- Duration of response (DOR) assessed by ICR(Up to 5 years)
- DOR as assessed by local investigator(Up to 5 years)
- Incidence of TEAEs(Up to 2 years)
- Change in treatment related symptoms as measured by EORTC-QLQ-C30(Up to 5 years)
- Change in treatment-related symptoms as measured by the FACT-LymS(Up to 5 years)
- Odronextamab concentrations in serum when administered with chemotherapy(Up to 30 months)
- Odronextamab concentrations in serum when administered as monotherapy(Up to 30 months)
- Event-free survival (EFS) as assessed by ICR(Up to 5 years)
- EFS as assessed by local investigator(Up to 5 years)
- Change in Patient Global Impression of Severity (PGIS)(Up to 5 years)
- Time to next anti-lymphoma treatment (TTNT)(Up to 5 years)
- Severity of TEAEs(Up to 2 years)
- Change in patient-reported general health status per EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)(Up to 5 years)
- Change in patient-reported lymphoma disease as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS)(Up to 5 years)
- Change in Patient Global Impression of Change (PGIC)(Up to 5 years)
- Change in score of the FACT-G GP5 item in the patient population(Up to 5 years)