Genmab and AbbVie’s Chemotherapy-Free Epcoritamab Combination Achieves Major Phase 3 Win in Relapsed/Refractory DLBCL
On June 29, 2026, Genmab A/S and AbbVie announced positive topline results from the Phase 3 EPCORE DLBCL-4 trial (NCT06508658), demonstrating that a chemotherapy-free combination of subcutaneous epcoritamab (EPKINLY/TEPKINLY) and oral lenalidomide significantly improves outcomes for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
The global, open-label, randomized trial compared the epcoritamab-lenalidomide combination against standard-of-care chemoimmunotherapy (R-GemOx: rituximab plus gemcitabine plus oxaliplatin) in adult patients who had received at least one prior line of systemic therapy and were ineligible for autologous stem cell transplantation (ASCT) or CAR-T cell therapy.
The trial met its primary endpoint of progression-free survival (PFS) with high statistical and clinical significance:
- Under U.S. censoring rules, the combination reduced the risk of disease progression or death by 60% (Hazard Ratio [HR] of 0.40 [95% CI 0.30, 0.55]; p-value <0.0001).
- Under non-U.S. censoring rules, the combination reduced the risk of disease progression or death by 56% (HR of 0.44 [95% CI 0.33, 0.60]; p-value <0.0001).
The safety profile of the combination was consistent with the established profiles of the individual agents, which are already approved for other lymphoma indications (epcoritamab is a CD3xCD20 T-cell engaging bispecific antibody, and lenalidomide is an immunomodulatory drug).
Daejin Abidoye, M.D., vice president and therapeutic area head of oncology at AbbVie, stated:
"Today's encouraging topline results highlight the potential of epcoritamab, a fixed-treatment therapy, in combination with lenalidomide, as a meaningful treatment option after initial disease progression."
This success positions the chemotherapy-free regimen as a potent second-line option, challenging traditional chemo-heavy salvage regimens in a highly aggressive hematologic malignancy. The companies plan to present full data at an upcoming medical meeting and engage global regulatory authorities regarding supplemental filings.