On May 19, 2023, epcoritamab-bysp was granted accelerated approval by the U.S. Food and Drug Administration for treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL)–not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy.1 Epcoritamab is a bispecific CD20-directed CD3 T-cell engager.
Approval was based on findings from the multicenter EPCORE NHL-1 study (ClinicalTrials.gov identifier NCT03625037). In this trial, 148 patients received subcutaneous epcoritamab step-up dosing followed by 48 mg weekly and then every 2 and every 4 weeks. All patients had received prior therapy containing an anti-CD20 monoclonal antibody. Objective response on independent review committee assessment was achieved in 91 patients (61%, 95% confidence interval [CI] = 53%–69%), with a complete response in 56 patients (38%). The median duration of response was 15.6 months (95% CI = 9.7 months to not reached).
How It Is Used
The recommended regimen is epcoritamab given subcutaneously in 28-day cycles until disease progression or unacceptable toxicity. Step-up dosing in cycle 1 consisted of 0.16 mg on day 1, 0.8 mg on day 8, and 48 mg on days 15 and 22. This was followed by fixed dosing of 48 mg weekly in cycles 2 and 3, every 2 weeks in cycles 4 to 9, and then every 4 weeks on day 1 of subsequent cycles.
Product labeling provides instructions for management of cytokine-release syndrome and immune effector cell–associated neurologic toxicity syndrome (ICANS). Epcoritamab should be administered by a qualified health-care professional; patients should be hospitalized for 24 hours after the cycle 1 day 15 dose of 48 mg.
Among 157 patients in the EPCORE NHL-1 safety population, the most common adverse events of any grade were cytokine-release syndrome (51%), fatigue (29%), musculoskeletal pain (28%), injection-site reaction (27%), pyrexia (24%), and abdominal pain (23%). Adverse events led to discontinuation of treatment in 3.8% of patients and led to death in 3.8% of patients.
Epcoritamab has a boxed warning for cytokine-release syndrome and ICANS and warnings/precautions for infections, cytopenias, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving epcoritamab.
1. Epkinly (epcoritamab-bysp) injection, for subcutaneous use, prescribing information, Genmab A/S, May 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761324s000lbl.pdf. Accessed June 14, 2023.