Epcoritamab monotherapy or epcoritamab with lenalidomide as first-line therapy for patients with diffuse large B-cell lymphoma (EPCORE DLBCL-3): primary analysis of an open-label, multicentre, randomised, phase 2 trial.

We aim to evaluate the efficacy and safety of fixed-duration epcoritamab monotherapy versus epcoritamab with lenalidomide in this patient population.

我们旨在评估固定疗程的epcoritamab单药治疗与epcoritamab联合来那度胺在此患者群体中的疗效和安全性。

Methods

This open-label, multicentre, randomised, phase 2 trial was conducted at 44 hospitals across 11 countries in Europe and Asia.

这项开放标签、多中心、随机、二期试验在欧洲和亚洲11个国家的44家医院进行。

Patients had newly diagnosed, histologically confirmed CD20-positive large B-cell lymphoma, were ineligible for anthracycline-based chemoimmunotherapy (age ≥80 or ≥75 years with clinically significant comorbidities), had Ann Arbor stage II-IV disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

患者为新诊断的、组织学证实的CD20阳性大B细胞淋巴瘤患者，不符合葱环类药物化疗免疫治疗的条件（年龄≥80岁或≥75岁且有临床显著的合并症），Ann Arbor分期为II-IV期，且东部肿瘤协作组（ECOG）表现状态为0-2。

In stage 1, patients were randomly assigned (1:1) to epcoritamab monotherapy or epcoritamab with lenalidomide using a validated interactive response technology system and stratified by the International Prognostic Index (<3 vs ≥3) and ECOG performance status (0-1 vs 2).

在第1阶段，患者通过使用经过验证的交互式响应技术系统随机分配（1:1）接受epcoritamab单药治疗或epcoritamab联合来那度胺治疗，并根据国际预后指数（<3 vs ≥3）和ECOG体能状态（0-1 vs 2）进行分层。

Epcoritamab was administered subcutaneously using a two step-up dosing schedule (0·16 mg on cycle 1 day 1 and 0·8 mg on cycle 1 day 8), followed by full 48 mg doses once per week in 28-day cycles during cycles 1-3 and once every 4 weeks during cycles 4-12 for up to 12 cycles.

Epcoritamab通过皮下注射使用两步递增剂量方案（第1周期第1天0.16毫克和第1周期第8天0.8毫克），随后在第1-3周期的每28天周期内每周一次全剂量48毫克，在第4-12周期的每4周一次，最多治疗12个周期。

Lenalidomide (10 or 20 mg) was given orally once a day on days 1-21 of 28-day cycles for up to 12 cycles.

来那度胺（10或20毫克）每天口服一次，连续21天，28天为一个周期，最多进行12个周期。

Based on stage 1, one of the treatment regimens was selected for expansion in stage 2.

基于第一阶段的结果，选择了一种治疗方案在第二阶段进行扩展。

The primary endpoint was investigator-assessed complete response rate (as of the data cutoff on Dec 5, 2025; Lugano criteria) in the full analysis set (all randomly assigned patients in stage 1 and in all treated patients in stage 2).

主要终点是研究者评估的完全缓解率（截至2025年12月5日数据截止时；Lugano标准），在全分析集（所有第一阶段随机分配的患者以及第二阶段所有接受治疗的患者）中进行评估。

Safety was analysed in patients who received ≥1 dose of trial treatment.

安全性分析针对接受≥1剂试验治疗的患者进行。

This study is registered with ClinicalTrials.gov, NCT05660967 (active, not recruiting).

该研究已在ClinicalTrials.gov注册，注册号为NCT05660967（活动状态，目前不招募）。

Results

Between March 8, 2023, and May 14, 2025, 111 patients were assessed for eligibility (88 in stage 1 and 23 in stage 2) and 108 were treated.

在2023年3月8日至2025年5月14日期间，共有111名患者进行了资格评估（第一阶段88人，第二阶段23人），其中108人接受了治疗。

Median age was 83·0 years (IQR 80·0-86·0). 51 (47%) of 108 were male, 57 (53%) were female, and 87 (81%) were White.

中位年龄为83.0岁（四分位数间距80.0-86.0）。108名患者中有51名（47%）为男性，57名（53%）为女性，87名（81%）为白人。

In stage 1, 44 patients each were randomly assigned to epcoritamab monotherapy or epcoritamab with lenalidomide and two did not receive treatment.

在第一阶段，44名患者被随机分配接受epcoritamab单药治疗或epcoritamab联合雷莫芦单抗治疗，有两名患者未接受治疗。

At data cutoff, the complete response rate in stage 1 was 63·6% (95% CI 47·8-77·6; in 28 of 44 patients) in the epcoritamab monotherapy group and 45·5% (30·4-61·2; in 20 of 44) in the epcoritamab with lenalidomide group.

在数据截止时，第一阶段中，epcoritamab单药治疗组的完全缓解率为63.6%（95%置信区间47.8-77.6；44名患者中有28名），而epcoritamab联合来那度胺治疗组的完全缓解率为45.5%（95%置信区间30.4-61.2；44名患者中有20名）。

The most common treatment-emergent adverse events (grade ≥3) were infections (eight [18%] of 44 patients) and fatigue (six [14%]) with epcoritamab monotherapy versus neutropenia (17 [40%] of 42) and infections (16 [38%]) with epcoritamab with lenalidomide; with serious adverse events in 28 (64%) versus 34 (81%).

最常见的治疗相关不良事件（3级或以上）是感染（44名患者中有8名[18%]）和疲劳（6名[14%]），在epcoritamab单药治疗组中，与之相比，epcoritamab联合来那度胺治疗组中为中性粒细胞减少症（42名患者中有17名[40%]）和感染（16名[38%]）；严重不良事件分别为28名（64%）和34名（81%）。

Treatment-emergent deaths occurred in six (14%) patients in the monotherapy group (cytomegalovirus infection reactivation, COVID-19 pneumonia, SARS-COV-2 infection, tumour lysis syndrome, neuroendocrine tumour of the lung, tumour haemorrhage) and six (14%) in the combined group (pneumonia, COVID-19 pneumonia, sepsis, general physical health deterioration, multiple organ dysfunction syndrome, acute cardiac failure).

单药治疗组中有六名（14%）患者出现治疗相关死亡（巨细胞病毒感染复发、COVID-19肺炎、SARS-COV-2感染、肿瘤溶解综合征、肺神经内分泌肿瘤、肿瘤出血），联合治疗组中也有六名（14%）患者死亡（肺炎、COVID-19肺炎、败血症、一般健康状况恶化、多器官功能障碍综合征、急性心脏衰竭）。

Based on differences in complete response rates and safety, epcoritamab monotherapy was selected for stage 2 and one patient did not receive treatment.

基于完全缓解率和安全性的差异，epcoritamab单药治疗被选用于第二阶段，有一名患者未接受治疗。

In the epcoritamab monotherapy group, the complete response rate was 45·5% (24·4-67·8; in ten of 22) in stage 2 and 57·6% (44·8-69·7; in 38 of 66) across stages 1 and 2.

在epcoritamab单药治疗组中，2期的完全缓解率为45.5%（24.4-67.8；22人中有10人），1期和2期的完全缓解率为57.6%（44.8-69.7；66人中有38人）。

The most common treatment-emergent adverse events (grade ≥3) among all patients who received epcoritamab monotherapy were infections (16 [24%]), neutropenia (eight [12%]), and hypertension (seven [11%]); with serious adverse events in 46 (70%).

所有接受epcoritamab单药治疗的患者中最常见的治疗后不良事件（≥3级）是感染（16 [24%]），中性粒细胞减少症（八 [12%]）和高血压（七 [11%]）；有严重不良事件的为46人（70%）。

Treatment-emergent deaths occurred in two (3%) patients in stage 2 (multiple organ dysfunction syndrome and acute respiratory failure).

在第二阶段（多器官功能障碍综合征和急性呼吸衰竭），有两名（3%）患者出现了治疗相关死亡。

interpretation

Fixed-duration epcoritamab monotherapy showed promising complete response rates and a manageable safety profile in older adults with newly diagnosed DLBCL and comorbidities, with slight differences between stages 1 and 2.

固定疗程的epcoritamab单药治疗在老年新诊断的DLBCL和合并症患者中显示出有希望的完全缓解率和可管理的安全性特征，第一阶段和第二阶段之间略有差异。

Continued investigation of epcoritamab as a first-line chemotherapy-free treatment option is warranted.

作为一线化疗无关治疗选择，对epcoritamab的持续研究是必要的。

funding

Genmab and AbbVie.

Genmab和AbbVie。