A Phase 3, Multicenter, Randomized, Open-Label Trial to Evaluate the Safety and Efficacy of Epcoritamab + Rituximab and Lenalidomide (R2) Compared to Chemoimmunotherapy in Previously Untreated Follicular Lymphoma (EPCORE™FL-2)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Genmab
- 入组人数
- 1,095
- 试验地点
- 787
- 主要终点
- Arm A1 vs Arm B: Percentage of Participants who Achieve Complete Response rate at 30 months (CR30)
研究概览
简要总结
Follicular lymphoma (FL) is the second most common B-cell cancer and the most common type of cancer of lymphocytes. Unfortunately, this disease is incurable with conventional treatment and the disease recurs in almost all patients. This study will assess how safe and effective epcoritamab is in combination with lenalidomide and rituximab (R2) in treating adult participants with previously untreated FL. Adverse events and change in disease condition will be assessed.
Epcoritamab is an investigational drug being developed for the treatment of FL. Study doctors put the participants in 1 of 5 groups, called treatment arms. Each group receives a different treatment. Around 1095 adult participants with previously untreated FL will be enrolled in approximately 250 sites across the world.
Participants will receive R2 (intravenous [IV] infusion of rituximab (R) and oral capsules of lenalidomide) alone or in combination with subcutaneous injections of epcoritamab. Participants may also receive investigator's choice chemoimmunotherapy (CIT): IV infusion of obinutuzumab (G) and IV injections of cyclophosphamide, IV injections of doxorubicin, IV injections of vincristine, oral tablets of prednisone (CHOP) [G-CHOP]/ R-CHOP or G and IV infusion of bendamustine (Benda) [G-Benda]/R-Benda. The total treatment duration will be 120 weeks for all arms except A2, which is 24 weeks of treatment.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
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
- •Diagnosis of follicular lymphoma (FL).
- •Have CD20+, histologically confirmed classic FL (previously Grade 1 to 3a FL) at most recent representative tumor biopsy based on the local pathology report, according to the 5th edition of World Health Organization (WHO) Classification of Haematolymphoid Tumours.
- •Are willing and able to comply with procedures required in the protocol.
- •Must have stage, III, IV or II with bulky disease >= 7cm).
- •Must be in need of systemic treatment per investigator, as evidenced by meeting at least one of the Groupe d'Etude des Lymphomes Folliculaire (GELF) criteria.
- •Has one or more target lesions:
- •A positron emission tomography (PET)/computerized tomography (CT) scan demonstrating PET-positive lesion(s), and
- •>=1 measurable nodal lesion (long axis >1.5cm) or >=1 measurable extra-nodal lesion (long axis >1.0 cm) on CT scan or MRI
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Able to receive at least one of the standard of care chemoimmunotherapy (CIT) treatment regimens: [Arm B] at the discretion of the Investigator, and rituximab and lenalidomide (R2) [Arm C].
- •Have laboratory values meeting the criteria in the protocol.
排除标准
- •Had major surgery within 4 weeks prior to randomization.
- •Have active cytomegalovirus (CMV) disease.
研究组 & 干预措施
Arm A2: Epcoritamab + Lenalidomide and Rituximab (R2)
Participants will receive epcoritamab in combination with R2 (ER2), during the 24 week treatment duration.
干预措施: Rituximab (Drug)
Arm A1: Epcoritamab + Lenalidomide and Rituximab (R2)
Participants will receive epcoritamab in combination with R2 (ER2), followed by epcoritamab during the 120 week treatment duration.
干预措施: Epcoritamab (Drug)
Arm A1: Epcoritamab + Lenalidomide and Rituximab (R2)
Participants will receive epcoritamab in combination with R2 (ER2), followed by epcoritamab during the 120 week treatment duration.
干预措施: Lenalidomide (Drug)
Arm A2: Epcoritamab + Lenalidomide and Rituximab (R2)
Participants will receive epcoritamab in combination with R2 (ER2), during the 24 week treatment duration.
干预措施: Lenalidomide (Drug)
Arm B: Chemoimmunotherapy (CIT) Option A
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) [G-CHOP]/ rituximab (R)-CHOP during the 120 week treatment duration.
干预措施: Cyclophosphamide (Drug)
Arm B: Chemoimmunotherapy (CIT) Option A
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) [G-CHOP]/ rituximab (R)-CHOP during the 120 week treatment duration.
干预措施: Obinutuzumab (Drug)
Arm B: Chemoimmunotherapy (CIT) Option B
Participants will receive CIT Option B (G and bendamustine (Benda) [G-Benda]/R-Benda during the 120 week treatment duration.
干预措施: Rituximab (Drug)
Arm B: Chemoimmunotherapy (CIT) Option B
Participants will receive CIT Option B (G and bendamustine (Benda) [G-Benda]/R-Benda during the 120 week treatment duration.
干预措施: Prednisone (Drug)
Arm B: Chemoimmunotherapy (CIT) Option B
Participants will receive CIT Option B (G and bendamustine (Benda) [G-Benda]/R-Benda during the 120 week treatment duration.
干预措施: Obinutuzumab (Drug)
Arm A1: Epcoritamab + Lenalidomide and Rituximab (R2)
Participants will receive epcoritamab in combination with R2 (ER2), followed by epcoritamab during the 120 week treatment duration.
干预措施: Rituximab (Drug)
Arm B: Chemoimmunotherapy (CIT) Option A
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) [G-CHOP]/ rituximab (R)-CHOP during the 120 week treatment duration.
干预措施: Prednisone (Drug)
Arm A2: Epcoritamab + Lenalidomide and Rituximab (R2)
Participants will receive epcoritamab in combination with R2 (ER2), during the 24 week treatment duration.
干预措施: Epcoritamab (Drug)
Arm B: Chemoimmunotherapy (CIT) Option A
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) [G-CHOP]/ rituximab (R)-CHOP during the 120 week treatment duration.
干预措施: Rituximab (Drug)
Arm B: Chemoimmunotherapy (CIT) Option A
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) [G-CHOP]/ rituximab (R)-CHOP during the 120 week treatment duration.
干预措施: Doxorubicin (Drug)
Arm C: Lenalidomide and Rituximab (R2)
Participants will receive lenalidomide and rituximab (R2) during the 120 week treatment duration.
干预措施: Rituximab (Drug)
Arm B: Chemoimmunotherapy (CIT) Option A
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) [G-CHOP]/ rituximab (R)-CHOP during the 120 week treatment duration.
干预措施: Vincristine (Drug)
Arm B: Chemoimmunotherapy (CIT) Option B
Participants will receive CIT Option B (G and bendamustine (Benda) [G-Benda]/R-Benda during the 120 week treatment duration.
干预措施: Bendamustine (Drug)
Arm C: Lenalidomide and Rituximab (R2)
Participants will receive lenalidomide and rituximab (R2) during the 120 week treatment duration.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Arm A1 vs Arm B: Percentage of Participants who Achieve Complete Response rate at 30 months (CR30)
时间窗: Up to 30 Months
CR30 will be determined by positron emission tomography-computerized tomography (cat scan) \[PET-CT\] per Lugano 2014 criteria, as assessed by independent review committee (IRC).
Arm A1 vs Arm B: Number of Participants with Progression-free survival (PFS)
时间窗: Up to 10 Years
PFS is defined as the time from randomization until disease progression determined by Lugano 2014 criteria per IRC, or death, whichever occurs first.
次要结局
- Arm A1 vs Arm B: Percentage of Participants with Change in CR Rate per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: Percentage of Participants with Change in CR Rate per IRC(Up to 10 Years)
- Arm A1 vs Arm C: Percentage of Participants with Change in CR Rate per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: TTNT per IRC(Up to 10 Years)
- Arm A1 vs Arm C: TTNT per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Time to Progression per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: Time-to-first PRO deterioration (TTD) in well-being using the lymphoma subscale (LymS) of FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm B: TTD in well-being using LymS of FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm C: TTD in well-being using LymS of FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm A2: Change in QoL as Measured by 5-Level European Quality of Life (EuroQol)-5-dimension [EQ-5D-5L](Up to 10 Years)
- Arm A1 vs Arm B: Change in QoL as Measured by EQ-5D-5L(Up to 10 Years)
- Arm A1 vs Arm C: Rate of MRD Negativity(Up to 10 Years)
- Arm A1 vs Arm A2: Change from Baseline in PF According to EORTC QLQ-C30(Up to 10 Years)
- Arm A1 vs Arm C: Change from Baseline in PF According to EORTC QLQ-C30(Up to 10 Years)
- Arm A1 vs Arm A2: OS(Up to 10 Years)
- Arm A1 vs Arm C: OS(Up to 10 Years)
- Arm A1 vs Arm B: Percentage of Participants who Achieve CR30(Up to 30 Months)
- Arm A1 vs Arm B: Number of Participants with PFS(Up to 10 Years)
- Arm A1 vs Arm A2: Percentage of Participants with Change in CR Rate per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: Percentage of Participants with Change in CR Rate per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: Percentage of Participants with Change in CR Rate per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: Time to Next Anti-lymphoma Therapy (TTNT) per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: TTNT per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: TTNT per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: Number of Participants with BOR per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: Number of Participants with Event-free Survival (EFS) per IRC(Up to 10 Years)
- Arm A1 vs Arm B: TTNT per IRC(Up to 10 Years)
- Arm A1 vs Arm B: TTNT per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Number of Participants with EFS per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: Number of Participants with EFS per IRC(Up to 10 Years)
- Arm A1 vs Arm B: Overall Survival (OS)(Up to 10 Years)
- Arm A1 vs Arm B: Rate of Minimal Residual Disease (MRD) Negativity Rate(Up to 10 Years)
- Arm A1 vs Arm B: Change from Baseline in Physical Functioning (PF) According to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ-C30)(21 Weeks)
- Arm A1 vs Arm A2: Rate of MRD Negativity(Up to 10 Years)
- Arm A1 vs Arm A2: Number of Participants with Best Overall Response (BOR) per per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Number of Participants with BOR per IRC(Up to 10 Years)
- Arm A1 vs Arm B: Number of Participants with BOR per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: Number of Participants with BOR per IRC(Up to 10 Years)
- Arm A1 vs Arm C: Number of Participants with BOR per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: Number of Participants with EFS per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: Number of Participants with EFS per IRC(Up to 10 Years)
- Arm A1 vs Arm C: Number of Participants with EFS per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Duration of Response (DOR) per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: DOR per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: DOR per IRC(Up to 10 Years)
- Arm A1 vs Arm B: DOR per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: DOR per IRC(Up to 10 Years)
- Arm A1 vs Arm C: DOR per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Duration of Complete Response (DOCR) per IRC(Up to 10 Years)
- Arm A1 vs Arm A2: DOCR per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: DOCR per IRC(Up to 10 Years)
- Arm A1 vs Arm B: DOCR per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: DOCR per IRC(Up to 10 Years)
- Arm A1 vs Arm C: DOCR per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Time to Progression per Investigator(Up to 10 Years)
- Arm A1 vs Arm B: Time to Progression per IRC(Up to 10 Years)
- Arm A1 vs Arm B: Time to Progression per Investigator(Up to 10 Years)
- Arm A1 vs Arm C: Time to Progression per IRC(Up to 10 Years)
- Arm A1 vs Arm C: Time to Progression per Investigator(Up to 10 Years)
- Arm A1 vs Arm A2: Number of Participants with Progression-free Survival After Subsequent Anti-Lymphoma Therapy (PFS2)(Up to 10 Years)
- Arm A1 vs Arm B: Number of Participants with PFS2(Up to 10 Years)
- Arm A1 vs Arm C: Number of Participants with PFS2(Up to 10 Years)
- Arm A1 vs Arm A2: Change in Tolerability as Measured by Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 10 Years)
- Arm A1 vs Arm B: Change in Tolerability as Measured by PRO-CTCAE(Up to 10 Years)
- Arm A1 vs Arm C: Change in Tolerability as Measured by PRO-CTCAE(Up to 10 Years)
- Arm A1 vs Arm A2: Change in Tolerability as Measured by The Functional Assessment of Cancer Therapy - General (FACT-G) Item GP5(Up to 10 Years)
- Arm A1 vs Arm B: Change in Tolerability as Measured by FACT-G Item GP5(Up to 10 Years)
- Arm A1 vs Arm C: Change in Tolerability as Measured by FACT-GG Item GP5(Up to 10 Years)
- Arm A1 vs Arm A2: Change in Symptoms as Measured by The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)(Up to 10 Years)
- Arm A1 vs Arm B: Change in Symptoms as Measured by FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm C: Change in Symptoms as Measured by FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm A2: Change in Quality of Life (QoL) as Measured by FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm B: Change in QoL as Measured by FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm C: Change in QoL as Measured by FACT-Lym(Up to 10 Years)
- Arm A1 vs Arm C: Change in QoL as Measured by EQ-5D-5L(Up to 10 Years)
- Arm A1 vs Arm A2: TTD in PF using the QLQ-C30 Physical Functioning Scale(Up to 10 Years)
- Arm A1 vs Arm B: TTD in PF using the QLQ-C30 Physical Functioning Scale(Up to 10 Years)
- Arm A1 vs Arm C: TTD in PF using the QLQ-C30 Physical Functioning Scale(Up to 10 Years)
- Arm A1 vs Arm A2: Change from baseline in the remaining items and domains of the EORTC QLQ-C30(Up to 10 Years)
- Arm A1 vs Arm B: Change from baseline in the remaining items and domains of the EORTC QLQ-C30(Up to 10 Years)
- Arm A1 vs Arm C: Change from baseline in the remaining items and domains of the EORTC QLQ-C30(Up to 10 Years)
- Arm A1 vs Arm A2: Change in Patient Global Impression of Change (PGIC) for General Lymphoma Symptoms(Up to 10 Years)
- Arm A1 vs Arm C: Change in PGIC for General Lymphoma Symptoms(Up to 10 Years)
- Arm A1 vs Arm A2: Change in Patient Global Impression of Severity (PGIS) for General Lymphoma Symptoms(Up to 10 Years)
- Arm A1 vs Arm B: Change in PGIS for General Lymphoma Symptoms(Up to 10 Years)
- Arm A1 vs Arm C: Change in PGIS for General Lymphoma Symptoms(Up to 10 Years)
- Arm A1 vs Arm A2: Percentage of Participants who Achieve CR30(Up to 30 Months)
- Arm A1 vs Arm C: Percentage of Participants who Achieve CR30(Up to 30 Months)
- Arm A1 vs Arm A2: Number of Participants with PFS(Up to 10 Years)
- Arm A1 vs Arm C: Number of Participants with PFS(Up to 10 Years)