EPCORE DLBCL-1 Trial Demonstrates Durable Responses, PFS Benefit With Epcoritamab in RR LBCL

Epcoritamab (Epkinly; AbbVie, Genmab) significantly improved progression-free survival (PFS) when compared with chemoimmunotherapy in patients with relapsed or refractory (RR) large B-cell lymphoma (LBCL), according to data from the phase 3 EPCORE DLBCL-1 trial (NCT04628494) presented at the European Hematology Association (EHA) 2026 Congress. Patients treated with epcoritamab experienced a 26% reduction in the risk of disease progression or death (HR, 0.74; 95% CI, 0.60-0.92; P = .0059), with 24-month PFS rates of 30% compared with 13% for chemoimmunotherapy.¹

Beyond delaying disease progression, epcoritamab produced deeper and more durable responses, with complete response rates (CRR) of 38% versus 26% and a median duration of response (DOR) of 37 months versus 6 months, respectively. Investigators noted that EPCORE DLBCL-1 is the largest randomized phase 3 trial conducted in RR LBCL and the first to demonstrate a statistically significant PFS benefit for a CD3×CD20 bispecific antibody monotherapy compared with combination chemoimmunotherapy.¹

Epcoritamab Expands Treatment Options in Relapsed/Refractory LBCL

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains curable for many patients treated with frontline chemoimmunotherapy. A substantial proportion of patients either relapse or develop refractory disease, indicating a need for effective therapies beyond conventional salvage treatment approaches.²

Prior data shows eligible patients have received salvage chemotherapy followed by autologous stem cell transplantation (ASCT), while CAR T-cell therapies have transformed outcomes for selected patients with relapsed disease. Despite these advances, many individuals remain ineligible for transplant or cellular therapy because of age, comorbidities, access barriers, or aggressive disease progression.³

Epcoritamab is a subcutaneously administered CD3×CD20 bispecific antibody that redirects T cells toward malignant B cells, resulting in targeted immune-mediated cytotoxicity. Unlike CAR T-cell therapies, epcoritamab is available off the shelf and does not require individualized manufacturing, making treatment initiation substantially faster.⁴

EPCORE DLBCL-1 Study Design

EPCORE DLBCL-1 evaluated epcoritamab monotherapy against chemoimmunotherapy consisting of rituximab (Rituxan; Genentech) plus gemcitabine (Gemzar; Eli Lilly) and oxaliplatin (Eloxatin, Sanofi-Aventis) (R-GemOx) or bendamustine (Bendeka; Teva Pharmaceuticals USA) plus rituximab (BR).¹

The trial had enrolled 483 patients with CD20-positive relapsed or refractory LBCL who were either ineligible for ASCT or had relapsed following transplant. Participants were randomized to receive epcoritamab (n = 241) or chemoimmunotherapy (n = 242).¹

The data population reflected a heavily pretreated group, with 73% of patients having received at least 2 prior lines of therapy, 34% receiving at least 3 prior lines, and nearly 70% demonstrating disease refractory to their most recent treatment. Prior stem cell transplantation had been performed in 15% of patients and 11% had previously received CAR T-cell therapy.¹

Durable Responses Drive Progression-Free Survival Benefit

Following more than 42 months of follow-up, epcoritamab demonstrated a statistically significant improvement in PFS compared with chemoimmunotherapy. Although overall response rates were similar between treatment groups (51% versus 48%), the quality and durability of responses strongly favored epcoritamab. Complete responses occurred in 38% of patients receiving epcoritamab compared with 26% receiving chemoimmunotherapy.¹

The durability findings were particularly notable. Median DOR reached 37 months with epcoritamab compared with only 6 months for chemo-immunotherapy. Additionally, median duration of complete response was not reached in the epcoritamab arm, whereas it was 11 months among patients receiving chemo-immunotherapy.¹

Researchers also reported a significant improvement in time to next treatment (TTNT), with a median TTNT of 7 months for epcoritamab compared with 4 months for chemo-immunotherapy.¹

Consistent with the observed improvements in response durability, fewer patients treated with epcoritamab required subsequent advanced therapies, including bispecific antibodies, CAR T-cell therapy, or stem cell transplantation (6% versus 26%, respectively).¹

Survival Findings and Safety Profile

Overall survival (OS) was not significantly different between treatment groups (HR, 0.96; 95% CI, 0.77-1.20). Investigators noted that OS outcomes may have been influenced by the widespread use of effective subsequent therapies among patients initially assigned to chemoimmunotherapy as well as COVID-19–related mortality during enrollment and follow-up.¹

Following post hoc adjustments accounting for subsequent novel therapies and COVID-19–related deaths, OS favored epcoritamab (adjusted HR, 0.76; 95% CI, 0.59-0.99).¹

The safety profile was generally consistent with prior studies of CD3×CD20 bispecific antibodies. Grade 3 or 4 infections occurred more frequently with epcoritamab than chemoimmunotherapy (30% versus 12%). Any-grade COVID-19 infections were reported in 36% and 11% of patients, respectively.¹

Cytokine release syndrome (CRS) occurred in 53% of patients receiving epcoritamab, although grade 3 events were uncommon at 3%. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 4% of patients, with grade 3 or 4 events reported in only 1%.¹

REFERENCES

1. Fox CP, Inchiappa L, et al. Results From EPCORE DLBCL-1: Randomized Phase 3 Study of Epcoritamab Versus Investigator's Choice Chemoimmunotherapy in Patients With Relapsed/Refractory Large B-Cell Lymphoma. Presented at: European Hematology Association Congress 2026; June 12, 2026; Stockholm, Sweden. Abstract EHA-2409. Accessed June 15, 2026.

2. Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-858. doi:10.1056/NEJMra2027612

3. National Comprehensive Cancer Network. Diffuse Large B-Cell Lymphomas. NCCN Clinical Practice Guidelines in Oncology. Version 4.2026. Accessed June 15, 2026. https://www.nccn.org/patients/guidelines/content/PDF/nhl-diffuse-patient.pdf

4. Epcoritamab-bysp (Epkinly) prescribing information. Genmab US Inc; 2025. Accessed June 15th, 2026. https://www.epkinlyhcp.com/