AbbVie and Genmab Secure FDA Approval for Epkinly Combination in Second-Line Plus Follicular Lymphoma

The FDA has approved AbbVie and GenMab’s Epkinly (epcoritamab-bysp) in combination with rituximab and lenalidomide (Epkinly + R²) for adults with relapsed or refractory (R/R) follicular lymphoma (FL).

Epkinly combination becomes first bispecific antibody regimen for relapsed or refractory follicular lymphoma

With this regulatory action, Epkinly becomes the first and only bispecific antibody combination therapy indicated for this patient population.¹

"Recurrent [FL] can be an incurable, complex and persistent disease, creating a clear need for additional treatments that can change its course earlier in the treatment journey," Lorenzo Falchi, MD, lymphoma specialist, department of medicine, Memorial Sloan Kettering Cancer Center, said in a press release. "The results shown with Epkinly + R² in the EPCORE FL-1 study are incredibly meaningful, demonstrating durable responses compared to patients treated with R² alone. These data, delivered by a regimen that's chemotherapy-free and can be administered in the outpatient setting, suggest that Epkinly + R² could potentially become a new standard of care."¹

Regulatory milestone expands Epkinly’s role in follicular lymphoma

In addition to the approval of the Epkinly combination therapy, the FDA also converted an accelerated approval granted in June 2024 to Epkinly monotherapy for R/R FL after two or more lines of systemic therapy to a full approval.² That action made Epkinly the first subcutaneous T-cell engaging bispecific antibody approved in the United States for this indication.

Bispecific T-cell engagement offers a differentiated therapeutic approach

Epkinly simultaneously attaches to the cluster of differentiation 3 (CD3) multimeric protein complex found on T cells, and cluster of differentiation 20 (CD20) found on B-cells. This action activates T cells to eliminate CD20 cells, which are prominent in patients with B-cell lymphomas.

In June 2023, Epkinly was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology as a third-line and subsequent therapy for patients with diffuse large B-cell lymphoma with disease progression following chimeric antigen receptor T-cell therapy or transplant, or no intent for transplant after the development of aggressive disease from indolent lymphoma.³

Phase 3 EPCORE FL-1 trial demonstrates substantial efficacy advantage

The latest approval of the Epkinly combination was based on the pivotal Phase III EPCORE FL-1 trial (NCT05409066).⁴

The open label, randomized, interventional trial compared the safety and efficacy of Epkinly plus R² vs. R² alone in patients with R/R FL. Patients were randomly assigned in a 1:1 ratio to receive the Epkinly combination (n=243) or R² alone (n=245). Epkinly was administered in 28-day cycles totaling 12 cycles overall or until disease progression or unacceptable toxicity, whichever occurred first.

The trial’s dual primary endpoints were progression-free survival (PFS) and overall response rate (ORR) as determined by Lugano 2014 criteria as assessed by Independent Review Committee.

Clinical outcomes show marked improvements with Epkinly combination

Results show that Epkinly plus R² lowered the risk of disease progression or death by 79% (HR 0.21, 95% CI: 0.13% - 0.33%, p<0.0001) vs. monotherapy.

For ORR, 89% of patients administered Epkinly plus R² responded to treatment (n=216/243, 95% CI: 84% - 93%; p<0.0001) vs. 74% of patients in the R² alone cohort (n=181/245, 95% CI: 68%-79%).

Median PFS was not reached (NR) in the Epkinly combination cohort (95% CI: 21.9 months - NR) vs. 11.2 months in the R² alone cohort (95% CI: 10.5 months - NR).

A total of 74% of patients in the Epkinly combination cohort achieved a complete response (n=181/243, 95% CI: 69% - 80%, p<0.0001) vs. 43% of patients in the R² alone cohort (n=106/245, 95% CI: 37% - 50%).

"With this approval, Epkinly is now the first bispecific antibody available for patients with follicular lymphoma in the second-line plus setting,” Daejin Abidoye, MD, vice president, therapeutic area head, oncology, solid tumor and hematology, AbbVie, said in the press release. “New options are needed to improve outcomes for patients with relapsed or refractory disease.”¹

References

1. AbbVie Announces U.S. FDA Approval of EPKINLY® (epcoritamab-bysp) in Combination with Rituximab and Lenalidomide for Relapsed or Refractory Follicular Lymphoma. News release. AbbVie. November 18, 2025. Accessed November 19, 2025. https://news.abbvie.com/2025-11-18-AbbVie-Announces-U-S-FDA-Approval-of-EPKINLY-R-epcoritamab-bysp-in-Combination-with-Rituximab-and-Lenalidomide-for-Relapsed-or-Refractory-Follicular-Lymphoma

2. EPKINLY® (epcoritamab-bysp) Approved by U.S. FDA for Patients with Relapsed or Refractory (R/R) Follicular Lymphoma (FL). Genmab. June 27, 2024. Accessed November 19, 2025. https://ir.genmab.com/news-releases/news-release-details/epkinlyr-epcoritamab-bysp-approved-us-fda-patients-relapsed-or

3. Genmab. Genmab Announces Epcoritamab Added to National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for ‘B-Cell Lymphomas’. News Release. June 22, 2023. Accessed November 19, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-epcoritamab-added-national-comprehensive-cancer

4. 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). ClinicalTrial.gov. July 28, 2025. Accessed November 19, 2025. https://clinicaltrials.gov/study/NCT05409066?intr=NCT05409066&rank=1