EPKINLY plus rituximab and lenalidomide (EPKINLY + R²) is now the first and only bispecific antibody combination therapy available for patients with relapsed or refractory follicular lymphoma after at least one line of systemic therapy
-   In the Phase 3 EPCORE^® FL-1 trial, EPKINLY + R² demonstrated significantly superior progression-free survival and overall response rates compared to standard of care R²with approximately 3 out of 4 patients achieving a complete response
-   Approval marks third indication for EPKINLY and first-ever FDA approval for a bispecific combination therapy in lymphoma

AbbVie announced that EPKINLY^® (epcoritamab-bysp), a T-cell engaging bispecific antibody administered subcutaneously, in combination with rituximab and lenalidomide (EPKINLY + R²) 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 + R² compared to standard of care R² and demonstrates the potential of this combination therapy to reshape FL treatment and to reach patients earlier in their treatment.ⁱ 

"Recurrent follicular lymphoma 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," said Lorenzo Falchi, M.D., lymphoma specialist, department of medicine, Memorial Sloan Kettering Cancer Center. "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."

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.^ii,iii The disease is considered incurable with current available therapies.^iv 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).^v

The Phase 3 EPCORE FL-1 study included a broad range of patients, including those with indolent to aggressive disease. In the study, EPKINLY + R² reduced 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 R² alone. In the dual primary endpoint of overall response rate (ORR), 89% of patients treated with EPKINLY + R² responded to treatment (n=216/243, 95% CI: 84% - 93%; p<0.0001) compared to 74% of patients treated with R² (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 + R² (95% CI: 21.9 months - NR) compared to 11.2 months for patients treated with R² (95% CI: 10.5 months - NR). Among patients who were treated with EPKINLY + R², 74% achieved a complete response (CR) (n=181/243, 95% CI: 69% - 80%, p<0.0001) compared to 43% of patients treated with R² (n=106/245, 95% CI: 37% - 50%).ⁱ

The safety profile of EPKINLY + R² in the EPCORE FL-1 study was generally consistent with the known safety profiles of the individual regimens (epcoritamab and R²).  The most common (≥ 20%) adverse reactions in patients who received EPKINLY + R² were 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. Please see additional Important Safety Information below.

"Today's milestone marks meaningful progress for people living with follicular lymphoma. With a bispecific-based therapy that can be administered in a variety of medical settings, patients have the possibility of accessing this treatment at sites of care closer to where they live," said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation.

EPKINLY + R² 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).

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

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.