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
- EPCORE DLBCL-2 is the first Phase 3 study of a bispecific antibody combination therapy to demonstrate statistically significant and clinically meaningful improvement in progression-free survival (PFS) in frontline diagnosed diffuse large B-cell lymphoma (DLBCL) patients
- Based on the topline results, Genmab and AbbVie will engage global regulatory authorities
NORTH CHICAGO, Ill. and COPENHAGEN, Denmark, Oct. 5, 2026 /PRNewswire/ -- AbbVie (NYSE: ABBV) and Genmab A/S (Nasdaq: GMAB) today announced positive topline results from the Phase 3 EPCORE DLBCL-2 trial evaluating fixed treatment duration epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, in combination with standard of care rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP), compared to R-CHOP alone, in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) score of 2 to 5. The trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in DLBCL patients with an IPI score of 2 to 5. The risk of disease progression or death was reduced by 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value 0.0001). The safety profile of epcoritamab when administered in combination with standard of care R-CHOP was generally well tolerated and consistent with the previously reported safety profiles of the individual agents (epcoritamab and R-CHOP).
"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," said Daejin Abidoye, MD, Vice President, Therapeutic Area Head, Oncology, Solid Tumor and Hematology, AbbVie. "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."
"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."
"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 diffuse large B-cell lymphoma," said Gilles Salles, MD, PhD, Chief of the Lymphoma Service and holder of the Steven A. Greenberg Chair at Memorial Sloan Kettering Cancer Center. "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."
This was the first planned efficacy interim analysis of the EPCORE DLBCL-2 study and, based on the significant benefit, the Independent Data Monitoring Committee (IDMC) recommended unblinding the study.
DLBCL is the most common type of non-Hodgkin lymphoma (NHL) worldwide, accounting for approximately 25-30 percent of all NHL cases. i,ii
Epcoritamab plus R-CHOP is an investigational combination not approved by regulatory authorities. AbbVie and Genmab will engage global regulatory authorities to determine next steps. Data will be submitted for presentation at a future medical meeting.
About the EPCORE® DLBCL-2 Trial
EPCORE DLBCL-2 (NCT05578976) is a global Phase 3 open label, multi-center, randomized trial to evaluate the efficacy of fixed duration, subcutaneous epcoritamab (GEN3013, DuoBody®-CD3xCD20) and standard of care rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) compared to R-CHOP alone in patients with newly diagnosed large B-cell lymphoma (DLBCL). The trial enrolled subjects with an International Prognostic Index (IPI) score of 2 to 5, including patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), high-grade B-Cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements, follicular lymphoma grade 3B (FL3B), T-cell/histiocyte-rich large B-Cell lymphoma (TCHR LBLC), and Epstein-Barr Virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL). The primary endpoint is PFS in participants with an International Prognostic Index (IPI) of 3-5 and the key secondary endpoint is PFS in total participants (IPI score of 2-5). The risk of disease progression or death for the primary endpoint population was reduced by 51% (HR 0.49 [95% CI 0.35, 0.69]; p-value 0.0001). Patients were randomized 2:1 to receive a fixed-duration regimen of epcoritamab plus R-CHOP for six cycles followed by epcoritamab alone for two cycles, or R-CHOP for six cycles followed by rituximab for two cycles. The trial started on February 8, 2023, and is ongoing.
More information on this trial can be found at https://clinicaltrials.gov/study/NCT05578976 (NCT: NCT05578976).
About Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) worldwide, accounting for approximately 25-30 percent of all NHL cases.iii,iv In the U.S., there are approximately 25,000 new cases of DLBCL diagnosed each year.v DLBCL can arise in lymph nodes as well as in organs outside of the lymphatic system, occurs more commonly in the elderly and is slightly more prevalent in men.vi,vii DLBCL is a fast-growing type of NHL, a cancer that develops in the lymphatic system and affects B-cell lymphocytes, a type of white blood cell. For many people living with DLBCL, their cancer either relapses, which means it may return after treatment, or becomes refractory, meaning it does not respond to treatment. Although new therapies have become available, treatment management can remain a challenge.iv,viii
About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.ix
Epcoritamab (approved under the brand name EPKINLY® in the U.S. and Japan, and TEPKINLY® in the EU) has received regulatory approval in certain lymphoma indications in more than 65 countries. Where approved, epcoritamab is a readily accessible therapy. Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies' oncology collaboration. The companies share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the relapsed or refractory (R/R) follicular lymphoma (FL) indication and additional approvals for the R/R diffuse large B-cell lymphoma (DLBCL) indication.
AbbVie and Genmab continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes a trial evaluating epcoritamab in combination with lenalidomide and rituximab (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.
What is EPKINLY?
EPKINLY is a prescription medicine used to treat adults with:
- certain types of diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma that has come back (relapsed) or that did not respond (refractory) after 2 or more treatments.
- follicular lymphoma (FL) that has come back or that did not respond to previous treatment, together with lenalidomide and rituximab
- follicular lymphoma (FL) that has come back or that did not respond after 2 or more treatments.
EPKINLY for the treatment of DLBCL is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY.
It is not known if EPKINLY is safe and effective in children.
IMPORTANT SAFETY INFORMATION
Important Warnings—EPKINLY can cause serious side effects, including:
- Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or lead to death. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
- Neurologic problems that can be serious, and can be life-threatening, and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
People with DLBCL or high-grade B-cell lymphoma may be hospitalized after receiving their first full dose of EPKINLY on Day 15 of Cycle 1 due to the risk of CRS and neurologic problems.