Epcoritamab/Lenalidomide Combo Cuts Progression Risk in R/R DLBCL

A chemotherapy-free regimen combining epcoritamab (Epkinly) and lenalidomide (Revlimid) significantly improved progression-free survival (PFS) compared with standard chemoimmunotherapy in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), according to topline results from the phase 3 EPCORE DLBCL-4 trial (NCT06508658).¹

The trial met its primary end point, with fixed-duration epcoritamab plus lenalidomide reducing the risk of disease progression or death by 60% (HR, 0.40; 95% CI, 0.30-0.55; P <.0001) and 56% (HR, 0.44; 95% CI, 0.33-0.60; P <.0001), based on differing censoring rules applied in the US and outside the US, respectively.

Regarding safety, the safety profile of epcoritamab in combination with lenalidomide was consistent with the previously reported safety profiles of each agent individually; no new safety signals were identified with the combination.

“These topline results add to the growing evidence supporting the versatility of epcoritamab-based combinations, including fixed-duration epcoritamab, across lines of therapy for patients with [R/R] large B-cell lymphoma [LBCL] who received at least [1] prior treatment,” Jan van de Winkel, PhD, CEO of Genmab, stated in a news release.¹ “With each new combination and treatment setting, we are building on our vision for epcoritamab as a core therapy across B-cell malignancies. We look forward to engaging with regulatory authorities as we continue to advance this program.”

About EPCORE DLBCL-4

EPCORE DLBCL-4 is a global, open-label, multicenter, randomized trial evaluating fixed-duration epcoritamab, a T-cell–engaging bispecific antibody administered subcutaneously, in combination with lenalidomide, against the chemoimmunotherapy regimen of rituximab (Rituxan), gemcitabine, and oxaliplatin (R-GemOx), in adult patients with R/R LBCL.² Eligible histologies included 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 LBCL, and Epstein-Barr virus–positive DLBCL.

Patients enrolled in the trial had received at least 1 prior line of systemic antineoplastic therapy that included an anti-CD20 monoclonal antibody–containing chemoimmunotherapy regimen, and had relapsed after, failed, or were not candidates for autologous stem cell transplant.

EPCORE DLBCL-4 is among several phase 3 trials in the broader EPCORE clinical program evaluating epcoritamab combinations across DLBCL and other B-cell malignancies. These include a trial of epcoritamab combined with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) in adult patients with newly diagnosed DLBCL (NCT05578976), and a trial of epcoritamab combined with lenalidomide and rituximab compared with chemoimmunotherapy in patients with previously untreated follicular lymphoma (NCT06191744).

Clinical Implications and Next Steps

The topline results from EPCORE DLBCL-4 reinforce a chemotherapy-free option for patients with R/R DLBCL who have progressed after initial anti-CD20–based therapy, a population that often has limited options outside of cellular therapy or further chemoimmunotherapy. The sponsors have announced plans to report detailed efficacy safety data to global regulatory authorities and at an upcoming medical meeting.

REFERENCES

1. Genmab Announces Positive Phase 3 Results for Epcoritamab Plus Lenalidomide in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma, Demonstrating Statistically Significant Improvement in Progression-Free Survival. News release. Genmab. June 29, 2026. Accessed June 30, 2026. https://tinyurl.com/37fjhw9v

2. 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 April 8, 2026. Accessed June 30, 2026. https://clinicaltrials.gov/study/NCT06508658