Epcoritamab Combo Therapy Shows High Response Rates in R/R Follicular Lymphoma Trial

AbbVie has unveiled updated findings from their ongoing EPCORE® NHL-2 clinical trial at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH) in North Chicago. This Phase 1b/2 trial is evaluating the efficacy of a fixed-duration combination treatment involving epcoritamab, lenalidomide, and rituximab (R2) in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). The trial included 111 participants with a median follow-up period exceeding two years. The results demonstrated a remarkable overall response rate (ORR) of 96% and a complete response (CR) rate of 87%.

Epcoritamab is a CD3xCD20 bispecific T-cell-engaging antibody administered subcutaneously. The data presented (Abstract #342) highlighted the potential of epcoritamab in combination with R2 to offer a durable and effective treatment for patients with relapsed or refractory follicular lymphoma, a typically slow-growing form of non-Hodgkin's lymphoma that represents 20-30% of all NHL cases. Despite being indolent, FL is notorious for recurring and transforming into a more aggressive form, diffuse large B-cell lymphoma (DLBCL), in over 25% of cases.

Mariana Cota Stirner, M.D., Ph.D., Vice President and therapeutic area head for hematology at AbbVie, emphasized the significance of these findings. She noted that the promising data supports the potential of epcoritamab as a core therapy for B-cell malignancies. The ongoing pivotal Phase 3 trial aims to further substantiate the efficacy of epcoritamab in combination with R2.

The EPCORE® NHL-2 trial protocol involved administering subcutaneous epcoritamab plus R2 for up to 12 cycles, followed by 12 additional cycles of epcoritamab monotherapy. Among the 111 participants, the study observed an estimated 89% of complete responders maintaining their CR at 18 months. Additionally, minimal residual disease (MRD) analysis revealed that 88% of the patients achieved MRD negativity, indicating no detectable disease at a 10-6 threshold.

However, the trial also reported some adverse events. COVID-19 infection was present in 57% of the patients, leading to discontinuation of epcoritamab in 13% of the cases and resulting in five fatalities. Other common treatment-emergent adverse events (TEAEs) included neutropenia (62%) and cytokine release syndrome (CRS; 51%). Most CRS events were low grade and resolved without leading to treatment discontinuation. One case of immune effector cell-associated neurotoxicity syndrome (ICANS) was reported but was also resolved.

AbbVie has not yet secured approval in the U.S., EU, or other territories for using epcoritamab in combination with R2 for FL. The safety and efficacy of this combination therapy continue to be evaluated. The U.S. Food and Drug Administration (FDA) recently granted a breakthrough therapy designation (BTD) for epcoritamab plus R2 for treating adult patients with R/R FL who have undergone at least one prior line of therapy. This combination is currently under further investigation in the ongoing Phase 3 EPCORE FL-1 trial.

The EPCORE® NHL-2 trial is a Phase 1b/2 open-label study designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of epcoritamab both as a monotherapy and in combination with standard care agents for B-cell non-Hodgkin's lymphoma. Epcoritamab is an IgG1-bispecific antibody created using Genmab's DuoBody® technology. It is engineered to bind simultaneously to CD3 on T cells and CD20 on B cells, triggering T-cell-mediated destruction of CD20+ cells.

Epcoritamab has been approved under the brand names EPKINLY® in the U.S. and Japan, and TEPKINLY® in the EU for certain lymphoma indications. Genmab and AbbVie are co-developing the drug as part of their oncology collaboration, with AbbVie responsible for global commercialization outside the U.S. and Japan. The companies are actively pursuing additional regulatory approvals for epcoritamab in various indications, including relapsed/refractory FL and DLBCL.

This ongoing research underscores the commitment of both companies to advance treatments for hematologic malignancies across multiple lines of therapy, with several Phase 3 trials currently in progress. The safety and efficacy of epcoritamab in these investigational uses are yet to be established.