EPKINLY + R2 was recently approved by the U.S. Food and Drug Administration as the first and only bispecific-based therapy for follicular lymphoma in the second-line setting
Genmab A/S announced primary data from the pivotal Phase 3 EPCORE FL-1 study evaluating fixed duration EPKINLY (epcoritamab-bysp) in combination with rituximab and lenalidomide (EPKINLY + R2) in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). The study showed that treatment with EPKINLY + R2 reduced the risk of disease progression or death by 79% (HR 0.21, 95% CI: 0.14-0.31, p<0.0001) compared to standard of care R2. Additionally, the overall response rate (ORR) in patients treated with EPKINLY + R2 was 95% (95% CI: 91.5, 97.4) compared to 79% in patients treated with R2 (95% CI: 73.6, 84.1; P<.0001). The EPCORE FL-1 study results were presented during an oral presentation (abstract 466) at the 67th Annual Meeting and Exposition of the American Society of Hematology (ASH) in Orlando, Florida, featured in the “Emerging Therapies and Immunotherapies in Blood Cancers” ASH press briefing.
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“Patients with relapsed or refractory follicular lymphoma have historically had limited treatment options,” said Lorenzo Falchi, M.D., Lymphoma Specialist, Department of Medicine, Memorial Sloan Kettering Cancer Center. “The EPCORE FL-1 results demonstrate that epcoritamab plus R2 is the first bispecific antibody-based, chemotherapy-free combination to show superior clinical benefit over standard of care in a Phase 3 trial, underscoring its potential to redefine the second-line treatment landscape for follicular lymphoma.”
The EPCORE FL-1 study included patients with R/R FL following at least one prior line of treatment across a broad range of patient characteristics and disease risk factors. Among patients who were treated with EPKINLY + R2 at the second planned interim analysis (median follow-up, 14.8 months), 83% achieved a complete response (CR) (n=201/243, 95% CI: 77.4, 87.3) compared to a 50% CR rate among patients treated with R2 (n=122/245, 95% CI: 43.4, 56.2). The 12-month duration of response (DOR) was 89% (95% CI: 83.6, 93.0) versus 49% (95% CI: 38.8, 57.5) for patients treated with EPKINLY + R2 and R2, respectively.
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The safety profile of EPKINLY + R2 in the EPCORE FL-1 study was consistent with the known safety profiles of the individual regimens (epcoritamab and R2). Grade 3 or 4 treatment-emergent adverse events (TEAE) were reported in 90.1% of patients treated with EPKINLY + R2 compared to 67.6% of patients treated with R2, the difference being primarily driven by higher rates of Grade 3 or 4 neutropenia (68.7% vs. 42.0%) and infections (33.3% vs. 15.1%). Fatal TEAEs occurred in 1.6% of patients treated with EPKINLY + R2 compared to 3.8% patients treated with R2. TEAEs leading to discontinuation occurred in 18.9% and 12.2% of patients treated with EPKINLY + R2 and R2, respectively. With the three step-up dosing regimen, CRS events were low grade and occurred in 26.3% of patients (21.2% Grade 1, 5.3% Grade 2).
“The pivotal results from the EPCORE FL-1 trial demonstrate the potential of epcoritamab, in combination with established therapies, to enable earlier intervention across sites of care and deliver improved outcomes for patients with relapsed or refractory follicular lymphoma,” said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. “We remain committed to developing epcoritamab, as a monotherapy and in combination, as a potential core therapy for B-cell malignancies and as a therapeutic innovation that can shift the treatment paradigm.”
In November 2025, the U.S. Food and Drug Administration (FDA) approved the combination of EPKINLY + R2 for the treatment of patients with relapsed or refractory FL after one or more lines of systemic therapy. EPKINLY is also approved in the U.S. to treat adults with relapsed/refractory FL after two or more prior treatments.
About the EPCORE FL-1 Trial
EPCORE FL-1 is a Phase 3 open-label interventional trial to evaluate the safety and efficacy of epcoritamab plus rituximab and lenalidomide (R2) versus R2 alone in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Patients were randomized to receive EPKINLY in combination with rituximab and lenalidomide (n=243) or rituximab and lenalidomide alone (n=245). Patients received EPKINLY in 28-day cycles for a total of 12 cycles or until disease progression or unacceptable toxicity, whichever occurred first. Efficacy was established based on the dual primary endpoints of progression free survival (PFS) and overall response rate (ORR) determined by Lugano 2014 criteria as assessed by Independent Review Committee (IRC). Additional efficacy outcome measures include complete response (CR) and duration of response (DOR).
About Follicular Lymphoma (FL)
Follicular lymphoma (FL) is typically an indolent, or slow-growing, form of non-Hodgkin lymphoma (NHL), that arises from B-lymphocytes. The second most common form of NHL, FL accounts for 20-30% of all NHL cases and is diagnosed in approximately 15,000 people in the U.S. every year.i,ii FL is considered incurable with current standard of care therapies.iii Patients often relapse, and with each relapse the remission and time to next treatment shorten.iv Over time, transformation to diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.
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Source- businesswire
