Epcoritamab receives FDA approval for patients with R/R DLBCL and HGBCL

On May 19, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval for the use of epcoritamab monotherapy in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBCL). Epcoritamab may be prescribed to patients with R/R DLBCL or HGBCL who have undergone at least two prior lines of systemic therapy.1

Epcoritamab is a bispecific CD3xCD20 T-cell-engaging antibody with cytotoxic activity against malignant CD20-positive B cells.1, 2 Upon crosslinking, the CD3–CD20 trimer triggers T-cell activation and expansion to induce T-cell cytotoxicity.2, 3 Previous results from the Phase I/II EPCORE NHL-1 study (NCT03625037) had demonstrated an anti-tumor effect of epcoritamab in patients with a range of refractory non-Hodgkin lymphoma (NHL) subtypes. Specifically in patients with R/R DLBCL, the study reported high overall response rates (ORRs) at multiple doses.4

The recent approval of epcoritamab is based on the Phase I/II EPCORE NHL-1 dose-escalation/dose-expansion study evaluating the drug’s efficacy in a cohort of 148 patients with R/R DLBCL and HGBCL.1 All enrolled patients had been pretreated with at least two lines of therapy.1, 2The primary endpoint was ORR. Results demonstrated an ORR of 61% (95% CI: 53, 69), with 38% of patients achieving a complete response (CR).1 The study further reported an estimated median duration of response (DOR) of 15.6 months (95% CI: 9.7, not reached) after a median follow-up of 9.8 months.1 The most common adverse events (AEs) included cytokine release syndrome (CRS), pyrexia, and fatigue.1, 2 FDA Boxed Warnings for epcoritamab include serious or life-threatening CRS and life-threatening or fatal immune effector cell-associated neurotoxicity syndrome (ICANS).1

At the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO), Umberto Vitolo, MD, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, discussed therapy options for highly refractory patients with NHLs such as DLBCL who have undergone multiple prior lines of therapy. In this interview, Prof. Vitolo states that “for many reasons […] we have some patients who are not eligible for [autologous stem cell transplantation (autoSCT) or CAR-T cell treatment] or [who] fail these procedures.” Prof. Vitolo thus emphasizes the importance of procuring agents to successfully treat this patient group and highlights the benefits of bispecific antibodies such as epcoritamab for this purpose.

Epcoritamab represents a rapid, deep, and durable therapy that is well tolerated by highly refractory patients with DLBCL and HGBCL. This new drug offers a promising avenue for patients who have undergone multiple prior lines of treatment.


  1. U.S. Food and Drug Administration. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. Available here (Last accessed 24/05/2023).
  2. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Journal of Clinical Oncology. 2023 Apr 20;41(12):2238–2247.
  3. Li T, Hiemstra IH, Chiu C, et al. Semimechanistic Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Informing Epcoritamab Dose Selection for Patients With B-Cell Lymphomas. Clinical pharmacology and therapeutics. 2022 Sep 27;112(5):1108–1119.
  4. Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. The Lancet.2021 Sept 25;398(10306):1157–1169.

Written by Alexandra Ertman
Edited by Elitsa Kamberska