FDA Grants Accelerated Approval to Epcoritamab-bysp for Relapsed or Refractory B-Cell Lymphoma

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On May 19, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the bispecific CD20-directed CD3 T-cell engager epcoritamab-bysp (Epkinly) for patients with 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.


Epcoritamab was evaluated in EPCORE NHL-1 ( identifier NCT03625037), an open-label, multicohort, multicenter, single-arm trial in patients with relapsed or refractory B-cell lymphoma. The efficacy population consisted of 148 patients with relapsed or refractory DLBCL–not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody–containing therapy.

The main efficacy outcome measure was overall response rate determined by Lugano 2014 criteria, as assessed by an Independent Review Committee. The overall response rate was 61% (95% confidence interval [CI] = 53%–69%), with 38% of patients achieving complete responses. With a median follow-up of 9.8 months among responders, the estimated median duration of response was 15.6 months (95% CI = 9.7 months to not reached).

Prescribing Details

The prescribing information has a Boxed Warning for serious or life-threatening cytokine-release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections and cytopenias. Among the 157 patients with relapsed or refractory large B-cell lymphoma who received epcoritamab at the recommended dose, cytokine-release syndrome occurred in 51% of patients, ICANS was reported in 6%, and serious infections in 15%.

Grade 1 cytokine-release syndrome occurred in 37% of patients, grade 2 occurred in 17%, and grade 3 occurred in 2.5%. Grade 1 ICANS occurred in 4.5% of patients, grade 2 occurred in 1.3%, and grade 5 occurred in 0.6%.

Epcoritamab should only be administered by a qualified health-care professional with appropriate medical support to manage severe reactions such as cytokine-release syndrome and ICANS. Because of the risk of cytokine-release syndrome and ICANS, patients should be hospitalized for 24 hours after the cycle 1, day 15 dosage of 48 mg.

The most common (≥ 20%) adverse reactions reported among patients were cytokine-release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3 or 4 laboratory abnormalities (≥ 10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

The recommended regimen consists of epcoritamab administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity. The recommended dose is step-up dosing in cycle 1 (0.16 mg on day 1, 0.8 mg on day 8, and 48 mg on day 15 and day 22). Step-up dosing is then followed by fixed dosing of 48 mg weekly dosing during cycles 2 through 3, every other week during cycle 4 through 9, and then every 4 weeks on day 1 of subsequent cycles.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.