Epcoritamab Monotherapy Yields Positive Results in Phase 3 R/R DLBCL Trial

The phase 3 EPCORE DLBCL-1 trial (NCT04628494) evaluating epcoritamab (Epkinly) in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) demonstrated an improvement in progression-free survival (PFS), complete response rate, duration of response, and time to next treatment in patients receiving epcoritamab monotherapy.^1,2

The full trial results will be submitted for presentation at a future medical meeting. Genmab, developer of the agent, and AbbVie intend to engage with global regulatory authorities to discuss the next steps.

Topline results show that epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, demonstrated an improvement in PFS in patients receiving epcoritamab monotherapy (HR, 0.74; 95% CI, 0.60–0.92). Overall survival was measured but deemed not statistically significant (HR, 0.96; 95% CI, 0.77–1.20).

The adverse events appeared to be consistent with the known safety profile of epcoritamab. Further analysis of the results is ongoing, including the potential impact of the increasing availability of novel anti-lymphoma therapies.

The global phase 3 study had a total enrollment of 483 patients with R/R DLBCL with at least 1 prior line of therapy. Of the total patients, 73% had received ≥2 prior lines of therapy. The study enrolled patients who were ineligible for high-dose chemotherapy and autologous stem cell transplant. Epcoritamab monotherapy was compared with the investigator’s choice of either rituximab (Rituxan) plus gemcitabine and oxaliplatin, or bendamustine plus rituximab.

Looking forward, data is anticipated in 2026 from the EPCORE DLBCL-2 (NCT05578976)³ and EPCORE DLBCL-4 (NCT06508658)⁴ trials, evaluating epcoritamab in combination with standard-of-care rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP), and epcoritamab in combination with lenalidomide (Revlimid) vs chemoimmunotherapy, respectively.

About the EPCORE DLBCL-2 and EPCORE DLBCL-4 Trials

The EPCORE DLBCL-2 trial is a phase 3 study investigating the change in disease activity of epcoritamab combined with intravenous and oral R-CHOP for the treatment of patients with newly diagnosed DLBCL. The study has an estimated enrollment of 900 patients and is estimated to be completed in 2029.³

The EPCORE DLBCL-4 trial is also a phase 3 study assessing the safety and efficacy of epcoritamab plus lenalidomide compared with rituximab plus gemcitabine and oxaliplatin in patients with R/R DLBCL. Approximately 360 patients will be enrolled and divided into 3 different treatment arms. The study is estimated to be completed in 2028.⁴

Epcoritamab has received regulatory approval in certain lymphoma indications in more than 65 countries and is approved in the US, Japan, and European Union.  Recently, epcoritamab was approved by the FDA for the treatment of patients with follicular lymphoma in November 2025.¹

“The EPCORE DLBCL-1 trial is the first [p]hase 3 study evaluating a bispecific antibody monotherapy to demonstrate improvements in [PFS] in patients with [R/R] DLBCL,” said Jan van de Winkel, PhD, CEO of Genmab, in a news release. “The results from this global trial contribute to the growing body of evidence supporting epcoritamab and build upon the robust foundation established by epcoritamab, which has been used to treat thousands of patients in need of additional therapeutic options. Together with our partner, AbbVie, we remain deeply committed to advancing the development of epcoritamab as a potential core therapy across a broad range of B-cell malignancies.”

REFERENCES

1.Genmab announces topline results for epcoritamab (DuoBody CD3xCD20) from phase 3 EPCORE DLBCL-1 trial in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). News release. Genmab. January 16, 2026. Accessed January 19, 2026. https://tinyurl.com/47j3etj2

2.A phase 3 trial of epcoritamab vs investigator’s choice chemotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (EPCORE DLBCL-1). ClinicalTrials.gov. Updated January 7, 2026. Accessed January 19, 2026. https://clinicaltrials.gov/study/NCT04628494

3.A study to evaluate change in disease activity of subcutaneous (SC) epcoritamab combines 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 January 23, 2025. Accessed January 19, 2026. https://clinicaltrials.gov/study/NCT05578976

4.A study of subcutaneously injected epcoritamab plus oral lenalidomide tablets compared to intravenously (IV) infused rituximab plus IV infused gemcitabine and IV infused oxaliplatin in adult participants with relapsed or refractory diffuse large B-cell lymphoma (EPCORE DLBCL-4). ClinicalTrials.gov. Updated January 7, 2026. Accessed January 19, 2026. https://clinicaltrials.gov/study/NCT06508658