AbbVie announced that EPKINLY(epcoritamab-bysp), a T-cell engaging bispecific antibody administered subcutaneously, in combination with rituximab and lenalidomide (EPKINLY + R) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). This approval of EPKINLY is based on results from the pivotal Phase 3 EPCORE FL-1 study that evaluated fixed duration EPKINLY + R compared to standard of care R and demonstrates the potential of this combination therapy to reshape FL treatment and to reach patients earlier in their treatment. FL is typically an indolent (slow-growing) form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes and impacts approximately 15,000 new patients per year in the U.S. The disease is considered incurable with current available therapies.
Patients with FL often relapse, and in some cases, the disease can transform into a more aggressive form of NHL called diffuse large B-cell lymphoma (DLBCL). The Phase 3 EPCORE FL-1 study included a broad range of patients, including those with indolent to aggressive disease. In the study, EPKINLY + Rreduced the risk of disease progression or death by 79% (HR 0.21, 95% CI: 0.13% - 0.33%, p<0.0001) compared to standard of care Ralone.
In the dual primary endpoint of overall response rate (ORR), 89% of patients treated with EPKINLY + Rresponded to treatment (n=216/243, 95% CI: 84% - 93%; p<0.0001) compared to 74% of patients treated with R (n=181/245, 95% CI: 68%-79%). The median for dual primary endpoint of progression-free survival (PFS), was not reached (NR) among patients treated with EPKINLY + R(95% CI: 21.9 months - NR) compared to 11.2 months for patients treated with R(95% CI: 10.5 months - NR). Among patients who were treated with EPKINLY + R, 74% achieved a complete response (CR) (n=181/243, 95% CI: 69% - 80%, p<0.0001) compared to 43% of patients treated with R(n=106/245, 95% CI: 37% - 50%).
The safety profile of EPKINLY + R in the EPCORE FL-1 study was generally consistent with the known safety profiles of the individual regimens (epcoritamab and R). The most common (= 20%) adverse reactions in patients who received EPKINLY + Rwere rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, cytokine release syndrome (CRS), pneumonia, COVID-19 and fever. The most common Grade 3 to 4 laboratory abnormalities (= 10%) were decreased neutrophil count, lymphocyte count, and platelets.
CRS occurred in 24% of patients at the recommended 3 step-up dosage schedule, and was primarily low grade (19% Grade 1, 5% Grade 2). A single event of immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in one patient, grade 1 (0.8%). The prescribing information has a Boxed Warning for serious or life-threatening CRS and ICANS.
Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. EPKINLY + R was previously granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of R/R FL. This designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).
In June 2024, EPKINLY monotherapy was granted accelerated approval by the FDA for the treatment of R/R FL following two or more lines of systemic therapy. With the results of the confirmatory Phase 3 EPCORE FL-1 study, the FDA has also converted this accelerated approval to a full approval. Both companies will pursue additional international regulatory approvals for the R/R FL indication.
Data from the Phase 3 EPCORE FL-1 study will be presented at the Annual Meeting and Exposition of the American Society of Hematology (ASH) in December 2025.
