FDA Approves Epkinly (epcoritamab-bysp) for Relapsed/Refractory Follicular Lymphoma
核心洞察
The FDA has granted accelerated approval to Epkinly (epcoritamab-bysp) for adult patients with relapsed or refractory follicular lymphoma (搜索) (FL) after two or more lines of systemic therapy.
Epkinly is the first and only T-cell engaging bispecific antibody administered subcutaneously approved in the U.S. for this patient population, offering a new treatment option.
The approval is based on Phase 1/2 EPCORE NHL-1 trial results, demonstrating an overall response rate of 82% and a complete response rate of 60% in R/R FL patients.
The U.S. Food and Drug Administration (FDA) has approved Epkinly (epcoritamab-bysp) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (搜索) (FL) after two or more lines of systemic therapy. This approval marks Epkinly as the first and only T-cell engaging bispecific antibody administered subcutaneously for this patient population in the U.S.
Clinical Efficacy and Safety
The approval is based on data from the Phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and preliminary efficacy of Epkinly in 127 adult patients with R/R FL. These patients had previously received a median of three lines of therapy, with 70% having double refractory disease. The trial demonstrated an overall response rate (ORR) of 82% and a complete response (CR) rate of 60%. Notably, 67% of patients achieved minimal residual disease (MRD) negativity. At a median follow-up of 14.8 months, the median duration of response (DoR) was not reached, indicating durable responses.
Jeff Sharman, MD, Disease Chair, Hematology Research, Sarah Cannon Research Institute (SCRI) at Willamette Valley Cancer Institute in Eugene, Oregon, noted, "Patients with relapsed or refractory follicular lymphoma (搜索) face significant treatment challenges, especially in third-line settings where there is currently no clear standard of care treatment. This approval and the durable responses observed in the follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, which reflected a real-world patient population, including patients with difficult-to-treat follicular lymphoma, demonstrate the potential of Epkinly for patients who face limited therapeutic options post-relapse."
Adverse Events
Common treatment-emergent adverse events (TEAEs) observed in the FL cohort of the trial (≥20%) included injection site reaction, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache. For patients receiving Epkinly at the recommended 3 step-up dosage schedule, CRS was primarily low grade (40% Grade 1, 9% Grade 2), with no grade 3 CRS events reported. The prescribing information includes a Boxed Warning for serious or life-threatening CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). Other warnings and precautions include infections, cytopenias, and embryo-fetal toxicity.
Follicular Lymphoma Context
Follicular lymphoma (搜索) (FL) is the second most common form of non-Hodgkin’s lymphoma (NHL), accounting for 20-30% of all NHL cases. Approximately 15,000 people develop FL each year in the U.S. While typically indolent, FL is considered incurable with current standard-of-care therapies, and patients often relapse. With each subsequent line of therapy, patients may experience shorter durability of response with currently available treatments.
Dosing and Administration
Epkinly is administered subcutaneously, utilizing a 3 step-up dosage regimen to mitigate the risk of cytokine release syndrome. This regimen and the observed durable responses have been achieved without mandatory hospitalization in clinical trials.
Ongoing Clinical Development
Genmab and AbbVie (搜索) are co-developing epcoritamab, with ongoing Phase 3 trials evaluating its use as a monotherapy and in combination with other therapies across various lines of treatment for hematologic malignancies. These trials include assessments in R/R DLBCL (NCT04628494), newly diagnosed DLBCL (NCT05578976), and R/R FL (NCT05409066), as well as previously untreated FL (NCT06191744).
NCCN Guidelines
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for B-Cell Lymphomas (Version 2.2024) have been updated to include Epkinly as a Category 2A, preferred recommendation for third-line and subsequent therapy for patients with FL.