FDA Approves Epcoritamab-Based Regimen in Follicular Lymphoma

The FDA has approved epcoritamab (Epkinly) plus rituximab (Rituxan) and lenalidomide (Revlimid; R²) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL).¹ This marks the first bispecific antibody combination available as a second-line treatment option in this patient population.

The approval is supported by positive data from the phase 3 EPCORE FL-1 study (NCT05409066). Here, the epcoritamab regimen reduced the risk of disease progression or death by 79% (HR, 0.21; P <.0001).

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 R² or R² alone. Along with the dual primary end points of progression-free survial (PFS) and overall response rate (ORR), secondary end points included percentage of patients achieving a complete response (CR), overall survival (OS), 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 FL 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.

Previous FDA Actions for Epcoritamab

In June 2024, the FDA granted accelerated approval to single-agent epcoritamab for the treatment of R/R FL following 2 or more prior lines of therapy, supported by theEPCORE NHL-1 study (NCT03625037).³ Data from the study which were presented at the 2023 American Society of Hematology Annual Meeting.⁴ Among 127 patients with FL that were enrolled to receive epcoritamab, the ORR was 82% (95% CI, 74.1%–88.2%) with a CR rate of 60%.The median PFS was 15.4 months, and the median duration of response, duration of CR, and OS were not reached by the data cut-off. Further, minimal residual disease negativity was associated with improved PFS.

In November 2023, the FDA granted epcoritamab breakthrough drug designation for FL.⁵

Epcoritamab is also indicated for the treatment of R/R diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after 2 or more lines of systemic therapy.⁶

REFERENCES

1. FDA approves epcoritamab-bysp for follicular lymphoma indications. US FDA. November 18, 2025. Accessed November 18, 2025. https://tinyurl.com/4s5u7r88

2. 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 November 12, 2025. https://tinyurl.com/3jtn38au

3. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. News release. FDA. June 26, 2024. Accessed November 12, 2025. https://tinyurl.com/dtu92zjh

4. Linton K, Jurczak W, Lugtenburg P, et al. Epcoritamab SC monotherapy leads to deep and durable responses in patients with relapsed or refractory follicular lymphoma: first data disclosure from the Epcore NHL-1 follicular lymphoma dose-expansion cohort. Blood. 2023;142(Suppl 1):1655. doi:10.1182/blood-2023-179887

5. Genmab announces positive regulatory updates for epcoritamab (Epkinly/Tepkinly) for the treatment of relapsed/refractory follicular lymphoma. News release. Genmab. November 27, 2023. Accessed November 12, 2025. https://tinyurl.com/5mprp34d

5. EPKINLY (epcoritamab-bysp) injection. US FDA. Accessed November 12, 2025. https://tinyurl.com/ywuth7p5