Epcoritamab plus R-CHOP reduced the risk of progression or death by 51% in newly diagnosed DLBCL in the Phase 3 EPCORE DLBCL-2 trial.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Genmab and AbbVie have reported positive topline results from the Phase 3 EPCORE DLBCL-2 trial evaluating fixed-duration epcoritamab in combination with R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The combination produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 51% compared with R-CHOP alone.
EPCORE DLBCL-2 is the first Phase 3 study of a bispecific antibody combination reported to demonstrate a statistically significant and clinically meaningful PFS benefit in frontline DLBCL, according to the companies. The epcoritamab plus R-CHOP regimen is investigational and is not approved by regulatory authorities for newly diagnosed DLBCL.
Phase 3 Trial Design
EPCORE DLBCL-2 (NCT05578976) is a global, randomized, open-label, multicenter Phase 3 trial. The study enrolled patients with newly diagnosed DLBCL and an International Prognostic Index (IPI) score of 2 to 5.
Patients were randomized 2:1 to receive either:
- Epcoritamab plus R-CHOP: six cycles of epcoritamab plus R-CHOP, followed by two cycles of epcoritamab alone.
- R-CHOP control: six cycles of R-CHOP, followed by two cycles of rituximab alone.
The primary endpoint was PFS in patients with an IPI score of 3 to 5. PFS in the overall population with an IPI score of 2 to 5 was the key secondary endpoint. Eligible histologies included DLBCL not otherwise specified, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, follicular lymphoma grade 3B, T-cell/histiocyte-rich large B-cell lymphoma and Epstein-Barr virus-positive DLBCL.
PFS Benefit Observed in Both Study Populations
The trial met its primary PFS endpoint in patients with an IPI score of 3 to 5. In this population, epcoritamab plus R-CHOP reduced the risk of disease progression or death by 51%, corresponding to a hazard ratio (HR) of 0.49 (95% CI, 0.35–0.69; P<0.0001).
The key secondary PFS endpoint was also met in the overall population with an IPI score of 2 to 5. In this population, the risk of progression or death was again reduced by 51%, with an HR of 0.49 (95% CI, 0.36–0.67; P<0.0001).
These findings indicate that adding fixed-duration epcoritamab to frontline R-CHOP substantially reduced the relative risk of progression or death compared with R-CHOP alone. However, the topline announcement does not yet provide median PFS, absolute PFS differences, overall survival results or detailed response data.
Safety Data Remain Limited
The companies described the safety profile of epcoritamab plus R-CHOP as generally well tolerated and consistent with the previously reported safety profiles of the individual agents.
However, the topline announcement did not provide detailed rates for adverse events. Additional data will therefore be needed to assess the full safety profile of the combination, including the frequency and severity of specific treatment-related toxicities.
Epcoritamab in B-Cell Lymphomas
Epcoritamab is a subcutaneous CD3xCD20 bispecific antibody designed to bind CD3 on T cells and CD20 on B cells, enabling T-cell-mediated killing of CD20-positive cells. The drug is approved under the brand name EPKINLY in the United States and Japan and TEPKINLY in the European Union for certain lymphoma indications. However, its combination with R-CHOP for newly diagnosed DLBCL remains investigational.
Genmab and AbbVie are also evaluating epcoritamab in other lymphoma settings and treatment combinations.
What the Results Mean
The EPCORE DLBCL-2 results are notable because R-CHOP has remained a standard frontline treatment for DLBCL for decades, while treatment advances in newly diagnosed disease have continued to be an important unmet need.
The 51% reduction in the risk of progression or death represents a substantial relative treatment effect. However, the available results are still topline and do not establish whether the PFS benefit will translate into longer overall survival or improved quality of life.
The study was open-label, and detailed subgroup, response and safety results have not yet been reported. Cross-trial comparisons with other frontline DLBCL regimens should also be avoided until complete datasets are available.
Genmab and AbbVie said they will engage global regulatory authorities to determine next steps, with detailed results planned for presentation at a future medical meeting.
Reference
Genmab and AbbVie Announce Epcoritamab in Combination with R-CHOP Demonstrates Statistically Significant Improvement in Progression-Free Survival in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma, Genmab, 05 October 2026
AbbVie and Genmab Announce Epcoritamab in Combination with R-CHOP Demonstrates Significant Improvement in Progression-Free Survival versus R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma, AbbVie, 05 October 2026
A Study to Evaluate Change in Disease Activity of Subcutaneous (SC) Epcoritamab Combined with Intravenous and Oral Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) or R-CHOP in Adult Participants with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) (EPCORE DLBCL-2), ClinicalTrials.gov ID NCT05578976
About the Writer
Neha Vishwakarma (LinkedIn) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.