Genmab’s EPCORE FL-1 Trial Meets Goals in R/R FL

Genmab A/S announced promising Phase 3 results from its EPCORE FL-1 clinical trial, which evaluated epcoritamab—a subcutaneous bispecific antibody—combined with rituximab and lenalidomide (R2) versus R2 alone in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL).

The study met both of its dual primary endpoints: overall response rate (ORR) and progression-free survival (PFS). Results showed a statistically significant improvement in both measures, with the combination therapy reducing the risk of disease progression or death by 79% (HR 0.21, p<0.0001). The findings are based on a pre-planned interim analysis and will be presented at the 67th American Society of Hematology (ASH) Annual Meeting, and will also support global regulatory submissions.

In a related development, the U.S. Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) for epcoritamab plus R2 on July 24, granting it priority review. The submission, also based on interim data, reported an ORR of 95.7% and PFS improvement (HR 0.21). A decision is expected by the FDA’s target action date of November 30, 2025. If approved, the combination would be the first bispecific antibody regimen available in the U.S. as a second-line treatment for R/R FL.

Dr. Jan van de Winkel, CEO of Genmab, highlighted the significance of the data:

“While therapeutic options exist for relapsed or refractory follicular lymphoma, effectiveness often declines with each treatment. These results—and the FDA’s decision to grant priority review—underline the potential of this combination therapy to significantly improve outcomes and reshape the treatment landscape.”

The safety profile of the epcoritamab and R2 combination remained consistent with existing safety data, with no new safety concerns observed. Epcoritamab already holds accelerated FDA approval as a monotherapy for adults with R/R FL after two or more prior treatments, and has received Breakthrough Therapy Designation for use in combination with R2 in patients who have received at least one prior therapy.

While not yet approved as a combination therapy in the U.S., EU, or other regions, epcoritamab with R2 continues to be evaluated in clinical trials for R/R FL.