Clinical Summary:

• Design/Population: The global, phase 3 EPCORE DLBCL-1 trial randomized patients with CD20-positive relapsed or refractory large B-cell lymphoma who were ineligible for autologous stem cell transplantation or had relapsed following transplantation to receive epcoritamab monotherapy or investigator’s choice chemoimmunotherapy. 
• Key Outcomes: Epcoritamab significantly improved progression-free survival compared with chemoimmunotherapy. Complete response rates were higher with epcoritamab, median duration of response was substantially longer, and time to next treatment improved. Overall survival was not significantly different in the primary analysis, although adjusted analyses accounting for COVID-19–related deaths and subsequent therapies favored epcoritamab. 
• Clinical Relevance: These findings establish epcoritamab as the first CD3×CD20 bispecific antibody monotherapy to demonstrate a statistically significant progression-free survival advantage over standard chemoimmunotherapy in this setting. 

Christopher Fox, MD, PhD, University of Nottingham, Nottingham, United Kingdom, discusses results from the phase 3 EPCORE DLBCL-1 trial evaluating epcoritamab monotherapy versus investigator’s choice chemoimmunotherapy in patients with relapsed or refractory large B-cell lymphoma. The study enrolled a heavily pretreated population, including patients with transformed follicular lymphoma, double-hit lymphoma, prior stem cell transplantation, and prior CAR T-cell therapy.

Epcoritamab significantly prolonged progression-free survival and produced deeper, more durable remissions than chemoimmunotherapy, with nearly 40% of patients achieving complete responses and almost 60% of complete responders remaining in remission at 3 years. Although the overall survival end point was not met, outcomes were likely influenced by COVID-19–related mortality and greater use of effective subsequent therapies—including CAR T-cell therapy, bispecific antibodies, and stem cell transplantation—in the control arm, while the safety profile remained consistent with prior experience.

Dr Fox presented these results at the European Hematological Association (EHA) Annual Meeting in Stockholm, Sweden. 

Transcript: 

Hello, my name is Chris Fox. I'm Professor of Haematology in Nottingham in the UK. Last Friday at the European Hematology Association meeting, on the 12th of June, I presented the first data from the EPCORE DLBCL-1 study that I'll now summarize some of the key findings for you. 

EPCORE DLBCL-1 is the largest randomized study ever conducted to date in relapsed or refractory DLBCL, and it focused on those patients who are ineligible for, or have relapsed following, autologous stem cell transplant. This was a large global phase 3 study, with 166 sites across approximately 24 countries.

Patients were randomized to, in the experimental arm, epcoritamab monotherapy given on the standard schedule in a treatment-to-progression fashion that we've become accustomed to, versus investigator's choice of chemoimmunotherapy. Within the study, nearly three-quarters of patients in the chemoimmunotherapy arm received R-GemOx as their chemoimmunotherapy, which has become adopted as a standard comparator arm in many of the recent randomized trials. The remaining minority received bendamustine and rituximab.  

This was a broad inclusion population, including transformed follicular lymphoma and double-hit lymphoma. This was also a heavily treated patient population. Approximately a quarter of patients had received 1 prior line of therapy and therefore entered the trial in the second-line setting, but three-quarters were more heavily treated, in the third-line or fourth-line setting and beyond, many of whom were primary refractory and/or refractory to subsequent lines of therapy. So this was a difficult population, with a median age of 72 years. There were dual primary end points: progression-free survival and overall survival. The study was powered separately for each end point, so only one of these had to be met for the study to be considered positive. 

The headline outcome was that progression-free survival was statistically and clinically superior in favor of the epcoritamab arm, with a 26% reduction in the risk of progressive disease or death for patients treated with epcoritamab. This corresponded to a hazard ratio of 0.74. We now have quite mature follow-up, with just over three and a half years of observation. When we look at the Kaplan-Meier plots for progression-free survival, we see a progressive separation of the curves, such that almost all patients in the chemoimmunotherapy arm had experienced disease progression or death by the 3 year mark.

The progression-free survival benefit translated into superior duration of response and duration of complete response. Looking at the headline data, nearly 40% of patients achieved a complete response with epcoritamab, and just under 60% of those patients remained in complete response at the 3 year mark. We also presented some data on the second-line population. This was a smaller subgroup within the trial, but again we saw clear superiority in terms of progression-free survival, raising the possibility that epcoritamab as a single agent could be useful in that patient group. 

We also discussed the key safety data, recognizing that safety reporting differs between a treatment-to-progression therapy and a shorter fixed-duration therapy, so we naturally have more safety information reported in the epcoritamab arm. There were more serious treatment-related adverse events in the epcoritamab arm, largely due to cytokine release syndrome. This was mainly low grade, with 17% grade 2 and 3% grade 3. We also saw more fatal adverse events in the epcoritamab arm, again recognizing the longer duration of safety reporting. More than half of these fatal adverse events were due to COVID-19, which coincided with recruitment during the Omicron phase of the pandemic. The remaining fatal adverse events were mainly due to infection.

In summary, we can see a significant progression-free survival advantage for this bispecific monotherapy. This is the first time that a bispecific monotherapy has been demonstrated in this way to be superior to chemoimmunotherapy. 

We did not see an overall survival benefit in favor of epcoritamab, and we think this was for 2 main reasons. One was early mortality, much of which was related to COVID-19, as mentioned. The second was that many more patients in the chemoimmunotherapy arm received an effective subsequent therapy following a progression-free survival event, including CAR T-cell therapy, bispecific antibodies, or stem cell transplantation. This occurred in 31% of patients in the chemoimmunotherapy arm versus only 6% of patients in the epcoritamab arm. We could clearly show that this had an impact on overall survival, and there are further data in the presentation slides if you want to refer to those from last week's EHA presentation. 

This is a significant study with clear benefit for patients treated with bispecific monotherapy, and I encourage you to find out more detail on this study and to look more broadly at the epcoritamab development program in DLBCL. 

Source: 

Fox CP, Inchiappa L, Ferhanoglu B, et al. Results from EPCORE DLBCL-1: Randomized phase 3 study of epcoritamab (Epcor) vs investigator’s choice chemoimmunotherapy (CIT) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-2409.