Genmab and AbbVie announced on October 5, 2026, positive topline results from the Phase 3 EPCORE DLBCL-2 trial evaluating epcoritamab, a subcutaneously administered T-cell engaging bispecific antibody, in combination with standard of care R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone) versus R-CHOP alone in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and an International Prognostic Index (IPI) score of 2 to 5.
The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with an IPI score of 3 to 5. The combination reduced the risk of disease progression or death by 51% in this primary endpoint population (HR 0.49 [95% CI 0.35, 0.69]; p-value <0.0001). Full efficacy data, including response rates and overall survival outcomes, were not disclosed in the topline announcement; the companies stated that data will be submitted for presentation at a future medical meeting.
Key finding
In the Phase 3 EPCORE DLBCL-2 trial, epcoritamab plus R-CHOP reduced the risk of disease progression or death by 51% versus R-CHOP alone in newly diagnosed DLBCL patients with an IPI score of 3 to 5 (HR 0.49 [95% CI 0.35, 0.69]; p<0.0001); however, the combination remains investigational and has not been approved by any regulatory authority.
Study Design
| Trial | EPCORE DLBCL-2 (NCT05578976); global Phase 3, open-label, multicenter, randomized; initiated February 8, 2023 |
|---|---|
| Population | Newly diagnosed large B-cell lymphoma patients with IPI score of 2–5, including DLBCL NOS, 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 EBV-positive DLBCL |
| Treatment | Epcoritamab plus R-CHOP for six cycles followed by epcoritamab alone for two cycles (2:1 randomization) vs. R-CHOP for six cycles followed by rituximab for two cycles |
| Primary endpoint | PFS in patients with IPI score of 3–5 |
| Key secondary endpoints | PFS in total enrolled population (IPI score of 2–5) |
The trial used a fixed-treatment-duration design and enrolled patients across multiple international sites. Patients were randomized 2:1 to the experimental arm. The trial remains ongoing.
Results and Safety
In the primary endpoint population (IPI 3–5), epcoritamab plus R-CHOP achieved a statistically significant improvement in PFS, with a hazard ratio of 0.49 (95% CI 0.35, 0.69; p<0.0001), representing a 51% reduction in the risk of disease progression or death. The key secondary endpoint — PFS in the total enrolled population with IPI scores of 2 to 5 — also demonstrated a statistically significant improvement, with a hazard ratio of 0.49 (95% CI 0.36, 0.67; p<0.0001). Numerical PFS rates, response rates, complete response rates, and overall survival data were not disclosed in the topline announcement.
The safety profile of the combination was described as generally well tolerated, and consistent with the previously established safety profiles of epcoritamab and R-CHOP individually. No additional safety detail, including rates of cytokine release syndrome or other adverse events of special interest, was provided in the topline release.
Clinical Context
R-CHOP has been the standard frontline treatment for DLBCL for approximately 25 years, and meaningful improvements in the first-line setting have proven difficult to achieve. According to the companies, EPCORE DLBCL-2 is the first Phase 3 trial of a bispecific antibody combination to demonstrate a statistically significant improvement in PFS in the frontline DLBCL setting, a distinction that investigators and company executives characterized as potentially practice-changing. Gilles Salles, MD, PhD, Chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center and a trial investigator, noted that the 51% risk reduction is “clinically meaningful and highly relevant to everyday practice.”
The companies indicated they will engage global regulatory authorities to determine next steps, though no submission timelines were specified. Epcoritamab plus R-CHOP remains an investigational combination. Key questions — including the durability of the PFS benefit, impact on overall survival, and outcomes across specific DLBCL subtypes enrolled in the trial — await full data disclosure at a future medical meeting.
Sources
- Genmab / AbbVie. “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.” Press release. October 5, 2026. View source.
AI disclosure: This article was prepared with assistance from generative AI using the source material cited above. It was reviewed and edited by Hailey Pash, MSN, APN, before publication.
