Epcoritamab Plus R-CHOP Improves PFS in Newly Diagnosed DLBCL

Topline results from the phase 3 EPCORE DLBCL-2 trial (NCT05578976) show that the addition of epcoritamab (Epkinly) to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) significantly improved progression-free survival (PFS) compared with R-CHOP alone in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).¹

The combination reduced the risk of disease progression or death by 51% compared with R-CHOP alone in the overall study population of patients with an International Prognostic Index (IPI) score of 2 to 5 (HR, 0.49; 95% CI, 0.36-0.67; P <.0001). The primary end point, PFS in patients with IPI scores of 3 to 5, was also met, with a 51% reduction in the risk of progression or death (HR, 0.49; 95% CI, 0.35-0.69; P <.0001).

Regarding safety, epcoritamab plus R-CHOP was generally well tolerated and consistent with the known safety profiles of the individual therapies.

"As an investigator with firsthand experience in both the landmark trial that established R-CHOP as a standard of care nearly 25 years ago and EPCORE DLBCL-2, it is particularly meaningful to see the potential benefit of bispecific antibody therapy in newly diagnosed [DLBCL],” said Gilles Salles, MD, PhD, chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, in a news release. “The 51% reduction in the risk of progression or death is clinically meaningful and highly relevant to everyday practice. These results have the potential to be practice-changing and could mark an important step forward in bringing the opportunity of cure to more patients.”

About EPCORE DLBCL-2

EPCORE DLBCL-2 is a global, randomized, open-label phase 3 trial evaluating fixed-duration subcutaneous epcoritamab plus R-CHOP vs R-CHOP alone in adults with newly diagnosed large B-cell lymphoma and IPI scores of 2 to 5.² The study included patients with 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.

Patients were randomly assigned 2:1 to receive epcoritamab plus R-CHOP for 6 cycles followed by epcoritamab monotherapy for 2 cycles, or R-CHOP for 6 cycles followed by rituximab for 2 cycles. The primary end point was PFS in patients with IPI scores of 3 to 5.

Implications for the Treatment Landscape

Epcoritamab is a CD3xCD20-directed bispecific antibody currently used in later-line treatment of B-cell lymphomas. Its evaluation in combination with R-CHOP represents an effort to move bispecific antibody therapy into the frontline setting for DLBCL.

For a disease in which R-CHOP has remained a foundational treatment for decades, these latest findings raise the possibility of further improving frontline outcomes by adding a targeted immune-based therapy to chemoimmunotherapy. The full efficacy and safety data will be important for determining the durability of benefit, patient populations most likely to benefit, and the potential place of epcoritamab plus R-CHOP in clinical practice.

The trial sponsors plan to engage with regulatory authorities regarding the results, bringing the field closer to determining whether epcoritamab could become part of a new frontline treatment approach for DLBCL.

REFERENCES

1. 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. News release. Genmab. October 5, 2026. Accessed October 6, 2026. https://tinyurl.com/4hvbpw8w

2. 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. Updated September 11, 2026. Accessed October 6, 2026. https://clinicaltrials.gov/study/NCT05578976