Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed or refractory follicular lymphoma (EPCORE FL-1): a global, open-label, randomised, phase 3 trial.

Lenalidomide and rituximab (R2) is an accepted standard of care in this population.

来那度胺和利妥昔单抗（R2）是这一人群中的公认标准治疗。

The EPCORE FL-1 trial aimed to evaluate the efficacy and safety of epcoritamab plus R2 versus R2 in participants with relapsed or refractory follicular lymphoma after at least one previous line of chemoimmunotherapy.

EPCORE FL-1试验旨在评估在至少接受过一种化疗免疫治疗方案失败后复发或难治性滤泡性淋巴瘤患者中，epcoritamab联合R2与单独R2治疗的疗效和安全性。

Methods

In this multicountry, open-label, phase 3 trial, participants were randomly allocated (1:1) to fixed-duration epcoritamab plus R2 or R2 for up to 12 cycles.

在这项多国、开放标签、III期试验中，参与者被随机分配（1:1）接受固定期限的epcoritamab联合R2或单独R2治疗，最多进行12个周期。

Epcoritamab was administered weekly in cycles 1-3 and every 4 weeks in cycles 4-12, lenalidomide once daily during cycles 1-12 (days 1-21), and rituximab weekly during cycle 1 and monthly in cycles 2-5.

Epcoritamab 在第1-3周期每周给药一次，在第4-12周期每4周给药一次，lenalidomide 在第1-12周期每天一次（第1-21天），rituximab 在第1周期每周给药一次，在第2-5周期每月给药一次。

The dual primary endpoints were overall response rate and progression-free survivalby independent review committee.

双重主要终点是独立评审委员会评估的总缓解率和无进展生存期。

The data reported here are from a planned interim analysis carried out after 78% of progression-free survivalevents had occurred.

这里报告的数据来自于一次计划中的中期分析，该分析是在78%的无进展生存事件发生后进行的。

This study is registered with ClinicalTrials.gov, NCT05409066, and EudraCT, 2021-000169-34, and is ongoing (closed to recruitment).

这项研究已在ClinicalTrials.gov上注册，注册号为NCT05409066，在EudraCT上注册，注册号为2021-000169-34，目前正在进行中（已停止招募）。

Results

Out of 668 participants screened for eligibility across 189 academic and non-academic centres in 30 countries across Africa, Asia, Australia, Europe, North America, and South America, a total of 488 participants were randomly allocated, 243 to epcoritamab plus R2 and 245 to R2.

在非洲、亚洲、澳大利亚、欧洲、北美和南美的30个国家的189个学术和非学术中心，共有668名参与者接受了资格筛查，最终有488名参与者被随机分配，其中243名分配至epcoritamab加R2组，245名分配至R2组。

The trial met its dual primary endpoints, showing superiority of epcoritamab plus R2 over R2 in overall response rate and progression-free survival. With a median follow-up of 14·8 months (IQR 11·4-19·0), overall response rate was 95% (95% CI 92-97) with epcoritamab plus R2 versus 79% (74-84; p<0·0001) with R2.

该试验达到了其双重主要终点，显示epcoritamab加R2在总缓解率和无进展生存期方面优于仅R2。中位随访时间为14.8个月（四分位数间距11.4-19.0），epcoritamab加R2的总缓解率为95%（95%置信区间92-97），而R2为79%（74-84；p<0.0001）。

Progression-free survivalwas longer with epcoritamab plus R2 versus R2 (hazard ratio0·21 [95% CI 0·14-0·31], p<0·0001); estimated 16-month progression-free survivalfavoured epcoritamab plus R2 (85·5% vs 40·2%).

与仅使用R2相比，epcoritamab联合R2治疗的无进展生存期更长（风险比0.21 [95%置信区间0.14-0.31]，p<0.0001）；估计的16个月无进展生存期epcoritamab联合R2治疗组更佳（85.5%对比40.2%）。

Grade 3 or higher adverse events were more frequent with epcoritamab plus R2 (219 [90%] of 243 participants) versus R2 (161 [68%] of 238 participants).

与仅使用R2相比，epcoritamab联合R2治疗的3级或更高级别的不良事件发生率更高（243名参与者中有219名[90%]对比238名参与者中有161名[68%]）。

Cytokine release syndrome was low grade with epcoritamab plus R2 (grade 1 in 28 [21%] participants and grade 2 in seven [5%] participants) and manageable, and all events were resolved.

细胞因子释放综合征在epcoritamab联合R2治疗中为低级别（1级在28名[21%]参与者中，2级在七名[5%]参与者中），且可控，所有事件均已解决。

interpretation

Epcoritamab plus R2 resulted in significantly higher response rate and longer progression-free survivalversus R2 among participants with follicular lymphoma who had received at least one line of therapy.

在至少接受过一线治疗的滤泡性淋巴瘤患者中，epcoritamab联合R2治疗相较于单独R2治疗，显著提高了反应率并延长了无进展生存期。

Epcoritamab plus R2 had more grade 3 or higher adverse events versus R2.

Epcoritamab联合R2治疗组与单独R2治疗组相比，出现3级或更高级别的不良事件更多。

Adverse events were manageable and consistent with the established safety profiles of the individual components, with no new safety findings identified.

不良事件是可管理的，并且与各个组成部分已知的安全性特征一致，没有发现新的安全问题。

These findings position epcoritamab plus R2 as a new standard of care for second-line or subsequent treatment of follicular lymphoma.

这些发现将epcoritamab联合R2定位为滤泡性淋巴瘤二线或后续治疗的新标准护理。

funding

AbbVie and Genmab.

AbbVie和Genmab。