Epcoritamab BLA To Be Submitted to FDA for Relapsed/Refractory LBCL

A biologics license application will be submitted to the FDA for subcutaneously administered epcoritamab (DuoBody®-CD3×CD20) as a treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL), according to a press release from Genmab.¹

The application will be supported by findings from the phase 1/2 EPCORE™ NHL-1 trial (NCT04663347), which featured a population of patients with B-cell non-Hodgkin lymphoma, including a cohort of patients with LBCL. Findings from the study were presented at 2022 European Hematology Association Congress and indicated that the single agent yielded clinically meaningful efficacy within the LBCL population.² In an LBCL expansion cohort of patients who has received at least 2 prior lines of systemic therapy, the overall response rate (ORR) was 63% with a complete response (CR) rate of 39%. Moreover, the ORR and CR rates in a group of patients who were naïve to CAR T-cell therapy were 69% and 42%, respectively, vs 54% and 34% in those who were previously treated with CAR T.

“Relapsed or refractory large B-cell lymphoma is often difficult to treat, and patients are in need of novel therapies that are effective, tolerable, and accessible,” Jan van de Winkel, PhD, chief executive officer at Genmab, said in a press release. “The results from the EPCORE NHL-1 trial, and other clinical trials evaluating epcoritamab in a variety of patients and treatment settings, have demonstrated that epcoritamab has the potential to offer people living with LBCL a new therapeutic advance with a manageable safety profile.”

The agent is a IgG1-bispecific antibody that was designed to achieve an immune response against target cell types through the use of cytotoxic T cells. Epcoritamab binds CD3 on T cells to CD20 on B-cells, resulting in the T-cell–mediated death of CD20-positive cells.

The study included a total of 157 patients with relapsed/refractory LBCL who received a median of 3 prior lines of therapy. Investigators reported a median duration of response (DOR) of 12.0 months after a median follow-up of 10.7 months. Moreover, the median DOR among complete responders was not reached and 89% of patients maintained CR at 9 months.

In terms of safety, most treatment-emergent adverse effects (TEAEs) occured in the first 12 weeks of treatment. Common any-grade TEAEs included cytokine release syndrome (CRS; 49.7%), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), diarrhea (20.4%), injection site reactions (19.7%), and anemia (17.8%). Additionally, frequent grade 3/4 TEAEs were neutropenia (14.6%), anemia (10.2%), neutrophil count decrease (6.4%), and thrombocytopenia (5.7%). The rate of high-grade CRS was low, with 2.5% of patients experiencing grade 3 events and no reported grade 4/5 events.

References

1. Genmab to submit biologics license application to U.S. Food and Drug Administration for epcoritamab (DuoBody®-CD3xCD20) for the treatment of relapsed/refractory large B-cell lymphoma (LBCL). News release. Genmab. June 30, 2022. Accessed July 6, 2022. https://bit.ly/3Ary1lB
2. Genmab announces late-breaking phase 2 trial results of investigational epcoritamab (DuoBody®-CD3xCD20) in relapsed/refractory large B-cell lymphoma (LBCL) patients presented at European Hematology Association (EHA) Presidential Symposium. News release. Genmab. June 11, 2022. Accessed July 6, 2022. https://bit.ly/3bSIigu