FDA Grants Approval to Epcoritamab for Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma and High-Grade Lymphoma

On May 19, 2023, the bispecific CD20-directed CD3 T-cell engager epcoritamab-bysp was granted accelerated approval from the Food and Drug Administration (FDA) as a treatment for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL from indolent lymphoma and high-grade B-cell lymphoma after ≥2 lines of previous therapy including an anti-CD20 monoclonal antibody therapy.  

This approval is based on the results of the multi-cohort, multicenter, single-arm EPCORE NHL-1 trial, which evaluated the efficacy of epcoritamab among patients with R/R DLBCL. Included in the trial were 157 patients with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma as well as high-grade B-cell lymphoma after 2 or more previous lines of therapy. Patients received epcoritamab with step-up dosing to 48 mg in cycle 1, followed by fixed dosing of 48 mg weekly during cycles 2 through 3, every other week during cycles 4 through 9, and every 4 weeks on day 1 of all subsequent cycles. The primary endpoint of this study was the overall response rate.

Within the efficacy cohort (n = 148) the overall response rate was 61%, with 38% of patients reaching complete responses. With a median follow-up duration of 9.8 months, The estimated median duration of response among responders was 15.6 months. 

The most common adverse events, observed in ≥20% of patients, were cytokine release syndrome (CRS), musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. Grade 3/4 laboratory abnormalities, which occurred in ≥10% of patients, included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets. They found that 15% of patients who experienced serious infections.

This approval comes with a Black Box label for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). In the EPCORE NHL-1 trial, 51% of patients experienced CRS and 6% experienced ICANS. Due to the risk of these severe reactions, the FDA recommends that patients who receive epcoritamab be hospitalized for 24 hours following the cycle 1, day 15 dose of 48 mg. 

Source: 

FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. US Food and Drug Administration; May 19, 2023. Accessed May 22, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell