Topline Findings
- Positive Phase III Trial Results: Genmab’s Epkinly (epcoritamab) combined with Rituxan (rituximab) and Revlimid (lenalidomide) (R2) showed promising efficacy in relapsed/refractory follicular lymphoma patients in the EPCORE FL-1 trial.
- Regulatory Milestones: The FDA granted Priority Review and Breakthrough Therapy Designation (BTD) for Epkinly plus R2, with a PDUFA date set for November 30, 2025.
- Potential to Transform Treatment: This bispecific antibody combination could reshape the follicular lymphoma treatment landscape by addressing unmet needs in patients with relapsed or refractory disease.
Results from the Phase III EPCORE FL-1 trial (NCT05409066) show that Genmab’s bispecific antibody Epkinly (epcoritamab) demonstrated promising efficacy when combined with Rituxan (rituximab) and Revlimid (lenalidomide) (R2) in patients with relapsed or refractory (R/R) follicular lymphoma (FL). According to the company, the combination showed statistically significant improvements in overall response rate (ORR) and progression-free survival (PFS).1
What is the Significance of Epkinly’s Trial Results for Patients with Relapsed or Refractory 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, Genmab, in a press release.
EPCORE FL-1 Trial Design and Endpoints
- The open-label EPCORE FL-1 trial evaluated the safety and efficacy of Epkinly plus R2 compared to R2 alone in 549 patients with R/R FL.
- The dual primary endpoints of the trial were ORR and PFS as assessed by independent review committee per Lugano criteria.
- Key secondary endpoints included but were not limited to the number of patients who achieved a complete response (CR), overall survival, PFS as assessed by investigator, duration of response, percentage of patients achieving minimal residual disease negativity, time to progression, duration of CR, and time to CR.1,2
Key Findings and Safety Profile
- Results showed that patients treated with Epkinly demonstrated a 79% reduction in risk of disease progression or death.
- Full data, derived from a pre-planned interim analysis, will be presented at the upcoming American Society of Hematology meeting, which Genmab says will form the basis for regulatory submissions.
- The safety profile of the combination was reported to be consistent with the known safety profiles of each individual medicine, with no new safety signals identified.1
Regulatory Updates
The FDA has also accepted Genmab’s supplemental Biologics License Application (sBLA) for Epkinly plus R2 with Priority Review and Breakthrough Therapy Designation. The FDA has set a Prescription Drug User Fee Act target action date of November 30, 2025.1
Epkinly was first approved in May 2023 as the first and only T-cell engaging bispecific antibody for the treatment of adult patients with R/R diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B–cell lymphoma, after two or more lines of systemic therapies.3 In June 2024, the FDA expanded the approval as a monotherapy to include patients with R/R FL after two or more lines of systemic therapy.4
Disease Background
According to Orphanet, the prevalence of FL is approximately one in every 3,000 people. The median diagnosis age is between 60 and 65 years and the disease is extremely rare in children. At five years, the survival rate is between 80% and 90%.
The median rate of survival is between 10 and 12 years.5 According to Genmab, it’s the most common form of non-Hodgkin lymphoma, accounting for 20% to 30% of all cases. In the United States, approximately 15,000 people are diagnosed with FL annually and over 25% of all cases are likely to transform into DLBCL.1
Addressing Unmet Needs in R/R FL
“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 reinforces our shared commitment with AbbVie to advance epcoritamab as a potential core therapy across B-cell malignancies,” concluded van de Winkel, in the press release.
References
- Genmab Announces Phase 3 EPCORE® FL-1 Clinical Trial Met Dual Primary Endpoints in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL). Genmab. August 7, 2025. Accessed August 8, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-phase-3-epcorer-fl-1-clinical-trial-met-dual
- 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. Accessed August 8, 2025. https://clinicaltrials.gov/study/NCT05409066?intr=NCT05409066&rank=1
- FDA Approves Epkinly. Drugs.com. Accessed August 8, 2025. https://www.drugs.com/newdrugs/fda-approves-epkinly-epcoritamab-bysp-bispecific-antibody-adult-patients-relapsed-refractory-6019.html
- Epkinly (epcoritamab-bysp) Approved by U.S. FDA for Patients with Relapsed or Refractory (R/R) Follicular Lymphoma (FL). Drugs.com. Accessed August 8, 2025. https://www.drugs.com/newdrugs/epkinly-epcoritamab-bysp-approved-u-s-fda-patients-relapsed-refractory-r-r-follicular-lymphoma-fl-6319.html
- Follicular lymphoma. Orphanet. Accessed August 8, 2025. https://www.orpha.net/en/disease/detail/545
