Epcoritamab Plus R-CHOP Meets PFS End Point in Newly Diagnosed DLBCL

Treatment with epcoritamab-bysp (Epkinly) in combination with R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with R-CHOP alone in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and an International Prognostic Index (IPI) score of 3 to 5, meeting the primary end point of the phase 3 EPCORE DLBCL-2 trial (NCT05578976).¹

In the primary end point population of patients with an IPI score of 3 to 5, the addition of epcoritamab to R-CHOP reduced the risk of disease progression or death by 51% (HR, 0.49; 95% CI, 0.35-0.69; P < .0001).¹ In the overall population of patients with an IPI score of 2 to 5, assessed as the key secondary end point, the risk of disease progression or death was also reduced by 51% (HR, 0.49; 95% CI, 0.36-0.67; P < .0001).

According to a news release from Genmab and AbbVie, EPCORE DLBCL-2 is the first phase 3 study of a bispecific antibody combination therapy to demonstrate a statistically significant and clinically meaningful improvement in PFS in patients with frontline DLBCL.

"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,” Gilles Salles, MD, PhD, chief of the Lymphoma Service and holder of the Steven A. Greenberg Chair at Memorial Sloan Kettering Cancer Center, stated 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.”

Data from EPCORE DLBCL-2 will be submitted for presentation at a future medical meeting. Genmab and AbbVie intend to share results from EPCORE DLBCL-2 with global health authorities.

“These topline results of epcoritamab in combination with R-CHOP mark the first Phase 3 study to demonstrate a statistically significant improvement in progression-free survival in patients with newly diagnosed DLBCL treated with a bispecific antibody combination and have the potential to reshape the frontline treatment landscape,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “While treatment advances have improved outcomes for patients with diffuse large B-cell lymphoma, options for newly diagnosed patients remain limited, reinforcing the need for additional therapies that can treat as many patients as possible in the frontline setting.”

What is known about the safety of the combination?

The safety profile of epcoritamab plus R-CHOP was generally well tolerated and consistent with the previously reported safety profiles of epcoritamab and R-CHOP as individual agents. Specific adverse effect (AE) data were not disclosed in the topline announcement.

How was EPCORE DLBCL-2 designed?

The global, open-label, multicenter, randomized phase 3 EPCORE DLBCL-2 trial enrolled patients 18 to 79 years of age with newly diagnosed, histologically confirmed CD20-positive DLBCL who were planned to receive 6 cycles of standard R-CHOP.² Eligible histologies included DLBCL not otherwise specified (NOS); high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL morphology; T-cell/histiocyte-rich large B-cell lymphoma; Epstein-Barr virus–positive DLBCL NOS; and grade 3B follicular lymphoma. Patients also needed an IPI score of 2 to 5 (with IPI 2 capped at approximately 30% of enrollment), an ECOG performance status of 0 to 2, at least 1 measurable PET-positive lesion, and a left ventricular ejection fraction of at least 50%. Prior systemic antilymphoma therapy for DLBCL, other than prephase corticosteroids with or without vincristine, was not permitted.

Patients were randomly assigned 2:1 to receive epcoritamab plus R-CHOP for 6 cycles followed by 2 cycles of epcoritamab monotherapy, or R-CHOP for 6 cycles followed by 2 cycles of rituximab monotherapy.¹ Treatment was administered in 21-day cycles.²

The primary end point was PFS per Lugano 2014 criteria by independent review committee in patients with an IPI score of 3 to 5. PFS in the overall population served as the key secondary end point, and additional secondary end points included event-free survival, complete remission rate at or after the end of treatment, overall survival, and minimal residual disease negativity rate.^1,2

“DLBCL is an aggressive disease and the need to advance treatment options is critical. These positive topline results suggest that epcoritamab combined with R-CHOP could offer a potential new standard of care in newly diagnosed DLBCL patients,” Daejin Abidoye, MD, vice president and therapeutic area head of Oncology, Solid Tumor and Hematology at AbbVie, added in a news release.¹ “The findings further strengthen our understanding and potential of bispecifics across the lymphoma treatment landscape, as we work to address urgent needs in this patient population.”

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 5, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-and-abbvie-announce-epcoritamab-combination-r-chop
2. A phase 3, randomized, open-label study to evaluate safety and efficacy of epcoritamab in combination with R-CHOP compared to R-CHOP in subjects with newly diagnosed diffuse large B-cell lymphoma (DLBCL). ClinicalTrials.gov. Accessed October 5, 2026. https://clinicaltrials.gov/study/NCT05578976