Epcoritamab Combo Shows Benefits in Phase 3 Follicular Lymphoma, Moves Toward FDA Approval

The phase 3 EPCORE FL-1 study (NCT05409066) met its dual primary end points of overall response rate (ORR) and progression-free survival, showing statistically significant and clinically meaningful improvements when epcoritamab (Epkinly) is combined with rituximab (Rituxan) and lenalidomide for the treatment of adult patients with relapsed/refractory follicular lymphoma.¹

Additionally, on July 24, 2025, the FDA accepted the supplemental biologics license application (sBLA) of epcoritamab plus rituximab and lenalidomide following at least 1 prior systemic therapy for priority review. The FDA has set a target action date of November 30, 2025. If approved, this regimen would be the first bispecific antibody combination available in the US as a second-line treatment option in follicular lymphoma.

“While therapeutic options exist for patients with relapsed or refractory follicular lymphoma, response rates tend to decline and durability diminishes with each subsequent line of treatment, which can increase the risk of the disease transforming into aggressive large-cell lymphoma,” said Jan van de Winkel, PhD, CEO of Genmab, in a press release. “The results from this trial and the decision from the FDA to accept the sBLA for priority review demonstrate the potential of this epcoritamab combination therapy to reshape the treatment landscape and reinforce our shared commitment with AbbVie to advance epcoritamab as a potential core therapy across B-cell malignancies.”

About the Phase 3 EPCORE FL-1 Study

Positive data from the EPCORE FL-1 trial support the global regulatory submissions of epcoritamab. Here, the epcoritamab regimen reduced the risk of disease progression or death by 79% (HR, 0.21; P <.0001). Full PFS and ORR data will be submitted for presentation at the 67^th Annual Meeting and Exposition of the American Society of Hematology (ASH) in December.

The study enrolled 549 patients across 273 global sites.² Patients were randomized to receive subcutaneous epcoritamab at 1 of 2 dose levels plus intravenous rituximab and oral lenalidomide or rituximab-lenalidomide alone. Along with the dual primary end points, secondary end points included percentage of patients achieving a complete response, overall survival, percentage of patients achieving measurable residual disease negativity, duration of response, duration of complete response, time to progression, time to next antilymphoma treatment, time to response, and event-free survival.

Patients were required to have an ECOG performance status of 0 to 2, histologically confirmed classic follicular lymphoma with no evidence of transformation to aggressive disease, relapsed or refractory disease to at least 1 prior systemic regimen containing an anti-CD20 monoclonal antibody and chemotherapy, and an estimated creatinine clearance of ≥50 mL/min. Those who were refractory to lenalidomide or had lenalidomide exposure within 12 months of randomization were not eligible for participation in the study.

In June 2024, the FDA granted accelerated approval to epcoritamab for the treatment of relapsed/refractory follicular lymphoma following 2 or more prior lines of therapy, supported by the EPCORE NHL-1 study (NCT03625037).³

REFERENCES:

1. Genmab Announces Phase 3 EPCORE® FL-1 Clinical Trial Met Dual Primary Endpoints in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL). News release. Genmab. August 7, 2025. Accessed August 8, 2025. https://tinyurl.com/3jtn38au

2. Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Follicular Lymphoma (EPCORE FL-1). ClinicalTrials.gov. Updated July 28, 2025. Accessed August 8, 2025. https://clinicaltrials.gov/study/NCT05409066

3. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. News release. FDA. June 26, 2024. Accessed August 8, 2025. https://tinyurl.com/dtu92zjh