Genmab’s Epcoritamab Plus R2 Maintains Strong Benefit Across Risk Groups in Relapsed Follicular Lymphoma

New data from a Genmab’s post-hoc subgroup analysis of the Phase 3 EPCORE FL-1 trial (NCT05409066) presented at the European Hematology Association (EHA) 2026 Congress further support the efficacy of fixed-duration epcoritamab plus rituximab and lenalidomide (R2) in patients with relapsed or refractory follicular lymphoma (FL).

The trial randomized 481 patients in the second-line or later setting, including 243 treated with epcoritamab plus R2 and 238 who received R2 alone. Investigators evaluated outcomes across clinically relevant subgroups, including Follicular Lymphoma International Prognostic Index (FLIPI) scores, progression of disease within 24 months of frontline therapy (POD24), and patient fitness measured by NHL-5 scores.

Mechanism of Action

Epcoritamab is a subcutaneous CD3xCD20 bispecific antibody developed using Genmab’s DuoBody® technology. By simultaneously targeting CD3-positive T cells and CD20-positive B cells, the therapy redirects T-cell activity against malignant B cells.

Efficacy Across Risk Groups

The analysis showed that progression-free survival (PFS) consistently favored epcoritamab plus R2 across all evaluated subgroups, with hazard ratios remaining below 0.30 regardless of baseline risk.

Key PFS hazard ratios included:

• FLIPI 0–2: HR 0.18
• FLIPI 3–5: HR 0.25
• POD24: HR 0.22
• NHL-5 low-risk: HR 0.27
• NHL-5 intermediate/high-risk: HR 0.14

The benefit observed in POD24 patients is particularly notable, as these individuals typically experience poorer long-term outcomes following early relapse.

Response rates also improved substantially with the addition of epcoritamab. Among patients with FLIPI scores of 0–2, overall response rates (ORR) reached 96.5% versus 84.8% with R2 alone, while complete response (CR) rates were 86.6% and 62.1%, respectively.

In patients with FLIPI scores of 3–5, ORR reached 93.0% with epcoritamab plus R2 compared with 72.6% for R2 alone. Complete response rates were 77.0% and 35.4%, respectively.

Deep responses were also observed across other clinically important populations. Complete response rates reached 85.5% versus 57.6% among non-POD24 patients, 81.3% versus 50.3% in NHL-5 low-risk patients, and 85.7% versus 49.0% in intermediate/high-risk NHL-5 patients.

Safety Profile

The safety profile remained consistent with findings from the overall EPCORE FL-1 population, with no new safety signals identified across subgroups.

Although neutropenia and infections were more frequently reported among patients receiving lower lenalidomide doses, the efficacy advantage of epcoritamab plus R2 was maintained, supporting the use of routine dose modifications to manage treatment-related adverse events.

Clinical Implications

Benoit Tessoulin, M.D., Ph.D., of Nantes University School of Medicine and University Hospital, said the findings support fixed-duration epcoritamab plus R2 as a treatment option for relapsed or refractory FL, demonstrating consistent efficacy and manageable tolerability across patient populations.

Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer at Genmab, said the analysis showed durable and deep responses regardless of baseline risk characteristics.

Development Path

The findings further strengthen the clinical evidence supporting epcoritamab in follicular lymphoma. Genmab and AbbVie continue to advance the bispecific antibody across multiple Phase 3 studies in B-cell malignancies, including diffuse large B-cell lymphoma and previously untreated follicular lymphoma, while pursuing additional regulatory opportunities in relapsed or refractory FL.

 Reference

Genmab Presents EPCORE® FL-1 Subgroup Data Demonstrating Consistent Efficacy and Safety Results for Epcoritamab in Combination with Rituximab and Lenalidomide (R2) Across Relapsed or Refractory (R/R) Follicular Lymphoma (FL) Patients – Genmab A/S