On November 18, 2025, the U.S. Food and Drug Administration (FDA) approved epcoritamab-bysp (Epkinly, Genmab / AbbVie) in combination with lenalidomide and rituximab (R²) for adults with relapsed or refractory follicular lymphoma (FL). The FDA also granted full approval for its monotherapy indication, previously under accelerated approval (2024).
Basis for Approval: EPCORE FL-1 Trial
The approval was supported by the EPCORE FL-1 trial (NCT05409066), a randomized, open-label study enrolling 488 patients with relapsed/refractory FL who received Epcoritamab + R² or R² alone.
- PFS Hazard Ratio: 0.21 (95% CI: 0.13–0.33; p<0.0001)
- Overall Response Rate (ORR): 89% (vs 74% in control)
- Median PFS: Not reached (vs 11.2 months in control arm)
Independent Review Committee (IRC) analysis confirmed significant superiority in both PFS and ORR for the epcoritamab combination arm.
Safety and Warnings
The label includes boxed warnings for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Infections (28%) and cytopenias were also common, with serious adverse reactions reported in 51% of patients.
Recommended Dosing
Epcoritamab is administered subcutaneously following a step-up dosing schedule (0.16 mg → 0.8 mg → 3 mg → 48 mg) during Cycle 1, followed by weekly 48 mg doses through Cycle 3, then every 4 weeks through Cycle 12.
Clinical Significance
This approval establishes epcoritamab, a CD20×CD3 bispecific antibody, as a key therapeutic option in the B-cell lymphoma space. As an off-the-shelf immunotherapy alternative to CAR-T, it expands treatment flexibility and accessibility for patients with relapsed or refractory FL.
This article was produced by the Morningglorysciences Editorial Team.
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