FDA Grants Approval to Epcoritamab for Patients With R/R Follicular Lymphoma

Key Clinical Takeaways:

• Primary takeway: The FDA granted new approval for epcoritamab-bysp with lenalidomide and rituximab for patients with relapsed/refractory follicular lymphoma.
• Secondary takeaway: The agency also converted epcoritamab’s accelerated monotherapy approval (2024) into a traditional approval for patients who received ≥2 prior systemic therapies.

On November 18, 2025, the US Food and Drug Administration (FDA) granted approval to epcoritamab-bysp (epcoritamab) with lenalidomide and rituximab (R2) for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL). 

The FDA also granted traditional approval to epcoritamab as a monotherapy for R/R FL after 2 or more lines of systemic therapy, after granting accelerated approval for this indication in 2024. 

EPCORE FL-1, a randomized, open-label trial that enrolled 488 patients with relapsed or refractory FL, led to the approval of epcoritamab-bysp with lenalidomide and rituximab. In this trial, eligible patients were randomized 1-to-1 to receive epcoritamab-bysp plus R2, or alternatively R2 alone. Patients had a median of 1 prior line of systemic therapy, while 24% and 17% had 2 and 3 or more prior lines, respectively.

Efficacy was established based on progression free survival (PFS) and overall response rate (ORR) as assessed by an independent review committee (IRC) using Lugano 2014 Criteria. The study demonstrated superiority of PFS and ORR in the epcoritamab-bysp arm. The PFS hazard ratio was 0.21 (95% CI, 0.13 to 0.33; p <0.0001). The median PFS was not reached (NR) (95% CI, 21.9 months to NR) in the epcoritamab-bysp arm and was 11.2 months (95% CI, 10.5 to NR) in the control arm. The ORR was 89% (95% CI, 84 to 93) in the epcoritamab-bysp arm and 74% (95% CI, 68 to 79) in the control arm.

As for adverse events and safety, prescribing information includes boxed warnings for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), as well as warnings and precautions for infections and cytopenias. Serious adverse reactions occurred in 51% of the patients in the epcoritamab-bysp arm, including serious infections in 28%. CRS occurred in 24% of patients, including serious CRS in 12%. ICANS occurred in 0.8%.

Source:

US Food and Drug Administration. Accessed November 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-epcoritamab-bysp-follicular-lymphoma-indications