BLA Submitted for Epcoritamab for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma, Large B-Cell Lymphoma

A Biologics License Application (BLA) has been submitted to the FDA for epcoritamab for the treatment of adult patients for epcoritamab (DuoBody-CD3xCD20; AbbVie and Genmab), an investigational subcutaneous bispecific antibody. The BLA for epcoritamab is for the treatment of adult patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) following 2 or more lines of systemic therapy.

Additionally, a Marketing Authorization Application was submitted to the European Medicines Agency for the drug in the treatment of adult patients with R/R diffuse LBCL (DLBCL) after 2 or more lines of systemic therapy.

Epcoritamab is being co-developed by both companies as part of their broad oncology collaboration. The companies continue to evaluate epcoritamab as a monotherapy and as a combination therapy across lines of therapy for a variety of hematologic malignancies.

Epcoritamab is an investigational IgG1-bispecific antibody developed with Genmab’s proprietary DuoBody technology, which is designed to direct cytotoxic T-cells to selectively produce an immune response toward target cell types. The antibody is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells to induce a T-cell mediated attack on CD20+ cells.

The regulatory submissions are supported by previously announced results from the LBCL cohort of the EPCORE NHL-1 open-label, multi-center phase 2 trial evaluating the safety and preliminary efficacy of epcoritamab in adult patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin lymphoma (NHL), including DLBCL.

"The regulatory submissions for epcoritamab exemplify our pursuit to deliver innovative care for people living with large B-cell lymphoma and diffuse large B-cell lymphoma who have limited treatment options," said Mohamed Zaki, MD, PhD, vice president and head, global oncology development, AbbVie, in a press release. "This achievement represents an initial step in our commitment to scientific research and providing an important treatment option with the potential to become a core therapy for people living with B-cell malignancies such as LBCL and DLBCL."

EPCORE NHL-1 included a phase 1 first-in-human, dose escalation part, a phase 2 expansion part, and an optimization part. The trial was intended to evaluate subcutaneous epcoritamab in patients with relapsed, progressive, or refractory CD20+ mature B-cell NHL, including LBCL and DLBCL. In the phase 2 expansion part, additional patients were treated with epcoritamab to further explore the safety and efficacy of epcoritamab in 3 cohorts of patients with different types of relapsed/refractory B-cell NHLs who had limited therapeutic options.

The study cohort included 157 individuals with relapsed or refractory large B-cell lymphoma (LBCL) who received at least 2 prior lines of systemic therapy. Approximately 38.9% of individuals received prior treatment with chimeric antigen receptor (CAR) T-cell therapy.

It consisted of 2 parts: a phase 1 first-in-human dose escalation and a phase 2 expansion.

The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL. The dose escalation findings, which are data recommended from the phase 2 dose, were published in The Lancet in 2021.

In the expansion part, additional individuals were treated with epcoritamab to further examine the efficacy and safety of the drug in 3 cohorts of individuals with different types of relapsed or refractory B-NHLs who had limited therapeutic options.

The results showed a confirmed overall response rate of 63.1%. The observed median duration was 12 months, and the mean lines of prior therapy of this cohort was 3.5, with the range being 2 to 11 lines of prior therapy.

The most common adverse events (AEs) of any grade included cytokine release syndrome (CRS), diarrhea, fatigue, neutropenia, and pyrexia.

The most common grade 3 or 4 AEs included anemia, decreased neutrophil count, neutropenia, anemia, and thrombocytopenia. Additionally, the observed grade CRS was 2.5%.

REFERENCE

AbbVie Announces Submissions of Regulatory Applications for Epcoritamab (DuoBody®-CD3xCD20) for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Large B-Cell Lymphoma (LBCL). October 28, 2022. Accessed October 31, 2022. https://news.abbvie.com/news/press-releases/abbvie-announces-submissions-regulatory-applications-for-epcoritamab-duobody-cd3xcd20-for-treatment-relapsedrefractory-diffuse-large-b-cell-lymphoma-dlbcl-and-large-b-cell-lymphoma-lbcl.htm