Tepkinly (epcoritamab) has received conditional marketing authorization from the European Commission (EC) as a monotherapy for treating adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) following two or more lines of prior therapy
It is the first and only subcutaneous bispecific antibody approved in the European Union (EU) for treating both R/R FL and R/R diffuse large B-cell lymphoma (DLBCL) after previous therapies have failed
The conditional approval for Tepkinly is based on findings from the Phase 1/2 EPCORE NHL-1 clinical trial, an open-label, multicenter, single-arm study that assessed the efficacy of Tepkinly as a monotherapy in patients with R/R FL who had undergone two or more prior systemic therapies. The trial included patients resistant to both anti-CD20 monoclonal antibody therapy and alkylating agents, with 70% showing double refractory disease. Moreover, 82% of patients were refractory to their last treatment, and 52% experienced disease progression within two years of starting any first systemic therapy.
The results revealed that 83% of patients treated with Tepkinly (n=128) achieved an overall response, with 63% achieving a complete response. The median duration of response was 21.4 months, with a median follow-up of 16.2 months. The duration of complete response had not been reached at the time of reporting.
Additionally, the study incorporated an optimization cohort, which involved 86 patients and focused on mitigating cytokine release syndrome (CRS) with a recommended three-step dosing strategy. Hospitalization was not required during the first cycle of treatment in this cohort. Results from this group showed that 40% of patients experienced Grade 1 CRS and 9% experienced Grade 2 CRS, with no cases of Grade 3 or higher CRS reported. Furthermore, no instances of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed in this cohort.
The safety profile of epcoritamab in the pivotal cohort was consistent with previous reports from the EPCORE NHL-1 DLBCL cohort. In a pooled analysis of the safety data from 382 patients, the most common adverse reactions (occurring in ≥20% of patients) included CRS, injection site reactions, fatigue, viral infections, neutropenia, musculoskeletal pain, fever, and diarrhea.
CRS was the most frequent serious adverse reaction, occurring in 34% of patients, and 14 patients (3.7%) experienced fatal adverse reactions, including pneumonia (in 2.4% of patients), viral infections (in 1.0%), and ICANS (in 0.3%).
About the Phase 1/2 EPCORE NHL-1 Trial The EPCORE NHL-1 trial is an open-label, multi-center study designed to evaluate the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (B-NHL), including FL. The trial consists of three parts: dose escalation, expansion, and optimization. The expansion phase aimed to further explore the safety and efficacy of epcoritamab in three different patient cohorts with limited treatment options. The optimization phase assessed alternative step-up dosing regimens to reduce the overall incidence and severity of CRS.
The primary endpoint for the expansion phase was the overall response rate, as evaluated by an independent review committee, with secondary endpoints including the duration of response, complete response rate, duration of complete response, progression-free survival, and time to response according to the Lugano criteria. The optimization phase primarily focused on the rate of ≥ Grade 2 CRS events and the overall incidence of CRS events from the first dose of epcoritamab through seven days following the second full dose.
About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody technology and administered subcutaneously. This technology is designed to direct cytotoxic T cells to target specific cell types and elicit an immune response. Epcoritamab binds simultaneously to CD3 on T cells and CD20 on B cells, triggering T-cell-mediated destruction of CD20+ cells.
Epcoritamab, known as Tepkinly in the European Union and EPKINLY in the United States, has been approved for certain lymphoma indications in several countries. It is co-developed by AbbVie and Genmab as part of their oncology collaboration. The two companies share commercial responsibilities in the U.S. and Japan, while AbbVie is responsible for global commercialization. They plan to seek additional regulatory approvals internationally for the treatment of R/R FL and R/R DLBCL.
Follicular lymphoma (FL) is a form of non-Hodgkin's lymphoma (NHL) that generally progresses slowly. However, it remains incurable, with around 13,000 new cases estimated each year in Western Europe. FL arises from B-lymphocytes and accounts for 20-30% of all NHL cases. The disease is notorious for recurring, and each relapse tends to shorten the duration of remission and the time before the next treatment is needed. Furthermore, FL can transform into diffuse large B-cell lymphoma (DLBCL), a more aggressive type of NHL that has worse survival outcomes. This transformation occurs in over 25% of FL patients.
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