FDA Approval Summary: Epcoritamab with Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma.

In November 2025, the U.S. FDA granted traditional approval to epcoritamab-bysp in combination with lenalidomide and rituximab (R2) for adults with relapsed or refractory follicular lymphoma (FL). Approval was based on EPCORE FL-1, a randomized, open-label trial evaluating fixed durations of epcoritamab in combination with R2 versus R2 alone in patients with relapsed or refractory FL. Efficacy was based on the dual primary endpoints of progression-free survival (PFS) and overall response rate (ORR), as assessed by an independent review committee (IRC). By intention-to-treat analysis (N=488), PFS was statistically significantly longer in the epcoritamab plus R2 arm, with a hazard ratio (HR) of 0.21 (95% CI: 0.13, 0.33) and p<0.0001 on first interim analysis. The median PFS was not reached (95% CI: 22, NR) in the epcoritamab plus R2 arm and was 11.2 months (95% CI: 10.5, NR) in the R2 arm. ORR per IRC was significantly higher in the epcoritamab plus R2 arm, based on prespecified analysis of the first 232 patients assessed (96% vs. 81% with R2;p<0.0001). This article summarizes key aspects of the regulatory review, including endpoint selection, randomized dose optimization, and a potential single-trial approach to support both accelerated and subsequent traditional approval.