Epcoritamab Added to NCCN Guidelines for Fast-Growing B-cell Lymphomas

Epcoritamab-bysp (epcoritamab, Epkinly; Genmab A/S and AbbVie) was added to the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a third-line and subsequent therapy for patients with diffuse large B-cell lymphoma (DLBCL) who have 1) disease progression following chimeric antigen receptor (CAR) T-cell therapy or transplant or 2) no intent for transplant following the development of aggressive disease from indolent lymphoma, according to a press release.

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“The NCCN Guidelines are a resource for treating various types of cancer and providing health care providers with information for making informed treatment decisions,” said Judith Klimovsky, executive vice president, chief development officer, Genmab, in the press release.

DLBCL is a fast-growing B-cell non-Hodgkin lymphoma (NHL) that accounts for approximately 30% of all NHL cases. Most patients with DLBCL—who tend to be older or male—experience relapsed or refractory disease (R/R DBLCL).

The T-cell engaging bispecific antibody is FDA-approved for adult patients with R/R DLBCL that is not otherwise specified (NOS). The indication includes patients with disease that originated from indolent lymphoma and patients with high-grade B-cell lymphoma (HGBL) following 2 or more lines of systemic therapy. The addition of the therapy to NCCN Guidelines is based on uniform consensus that epcoritamab is an appropriate treatment for aggressive DLBCL.

To receive further indications, epcoritamab must show clinical benefits in confirmatory trials. There are 3 phase 3 and open-label trials currently ongoing:

• NCT046284941 is evaluating epcoritamab as a monotherapy for patients with R/R DLBCL.
• NCT05578976 is evaluating the drug in a combination regimen for adult participants with newly diagnosed DLBCL.
• NCT05409066 is a clinical trial evaluating epcoritamab in a combination regimen for patients with R/R follicular lymphoma (FL).

In the clinical trial, at least 20% of patients experienced low-grade adverse events (AEs), including cytokine release syndrome, musculoskeletal pain, reaction at the injection site, pyrexia, and gastrointestinal issues. Investigators also observed grade 3 and 4 AEs (decreases in lymphocyte count; neutrophil count; white blood cell count; hemoglobin, and platelets) in 10% or more of patients.

In 2022, The European Medicines Agency and Ministry of Health, Labor and Welfare of Japan approved early applications (Marketing Authorization Application and new drug application, respectively) for epcoritamab for patients with R/R DLBCL who were previously treated with 2 or more lines of systemic therapy. Neither the European Union nor Japan have regulatory approvals yet, nor is it approved in the US to treat newly diagnosed DLBCL or R/R FL.

Epcoritamab is an Immunoglobulin G1 (IgG1)-bispecific antibody. It concurrently binds to the cluster of differentiation 3 (CD3) multimeric protein complex found on T cells, and cluster of differentiation 20 (CD20) found on B-cells. When epcoritamab binds to CD3 and CD20, it activates the T-cell to kill the CD20 cells, which are too numerous in patients with B-cell lymphomas.

Epcoritamab is subcutaneously administered to patients with R/R DLBCL using a proprietary technology (DuoBody, Genmab). It is designed in a way that allows the T cells to selectively target CD20+ cells and deliver an immune response.

“We are pleased that NCCN has updated its guidelines to include epcoritamab in a speedy manner,” Klimovsky said in the press release.

Reference

Genmab. Genmab Announces Epcoritamab Added to National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for ‘B-Cell Lymphomas’. News Release. June 22, 2023. Accessed June 29, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-epcoritamab-added-national-comprehensive-cancer