EMA Validates Application for Epcoritamab in Relapsed/Refractory Follicular Lymphoma


The European Medicines Agency has validated a type II application for the investigational T-cell engaging bispecific antibody epcoritamab-bysp for patients with relapsed/refractory follicular lymphoma following at least 2 prior lines of therapy

Mariana Cota Stirner, MD, PhD

Mariana Cota Stirner, MD, PhD

The European Medicines Agency (EMA) has validated a type II application for the investigational T-cell engaging bispecific antibody epcoritamab-bysp (Tepkinly) for patients with relapsed/refractory follicular lymphoma following at least 2 prior lines of therapy, according to a press release from AbbVie, which simultaneously announced that the FDA has granted a breakthrough therapy designation (BTD) to the agent for the same indication.1

These updates are supported by results from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).2 Findings from the follicular lymphoma cohort (n = 128) showed that epcoritamab led to an overall response rate (ORR) of 82% by independent review committee assessment, exceeding the prespecified threshold for efficacy in the trial. Notably, 70.3% of patients were double refractory to an anti-CD20 monoclonal antibody and an alkylating agent. The median duration of response (DOR) was not yet reached.2

"The FDA granted BTD and validated European application are an important step in our commitment to improving the lives of patients with relapsed/refractory follicular lymphoma, a complex blood cancer with limited treatment options," Mariana Cota Stirner, MD, PhD, vice president and therapeutic area head for hematology at AbbVie, said in a press release.1 "Together with Genmab, we are continuing to investigate epcoritamab as a potential core therapy for multiple B-cell malignancies, including diffuse-large B-cell lymphoma and now follicular lymphoma."

The investigational IgG1-bispecific antibody is designed to direct cytotoxic T cells selectively to induce an immune response and simultaneously bind to CD3 on T cells and CD20 on B cells. In turn, this induces T-cell–mediated killing of CD20-positive cells. Previously, epcoritamab received accelerated approval from the FDA for adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).3

Patients with a CD20-positive mature B-cell neoplasm who relapsed, progressed, and/or were refractory following treatment with an anti-CD20 monoclonal antibody in combination with chemotherapy and/or relapsed after autologous stem cell rescue were eligible for enrollment in the escalation phase. Additionally, patients must have had an ECOG performance status less than 2; measurable disease by CT, MRI, or PET-CT scan; and acceptable renal and liver function.4

Notably, at least 2 prior lines of antineoplastic therapy, including an anti-CD20 monoclonal antibody were required for enrollment in the expansion and optimization phases.4

Exclusion criteria for all parts included primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening; a past or current malignancy other than the inclusion diagnosis; alanine aminotransferase and/or aspartate aminotransferase greater than 3 times the upper limit of normal; a total bilirubin greater than 1.5 times the upper limit of normal, unless bilirubin rise was due to Gilbert's syndrome or was of non-hepatic origin; an estimated creatinine clearance less than 45 mL/min; known clinically significant cardiovascular disease; autoimmune disease resulting in permanent immunosuppression; prior therapy with an investigational bispecific antibody targeting CD3 and CD20; and prior treatment with CAR T-cell therapy within 30 days prior to the first dose of epcoritamab.4

The trial included 3 parts: the phase 1 first-in-human, dose-escalation part; the phase 2a expansion part; and the phase 2a dose-optimization part. In addition to follicular lymphoma and DLBCL, the study drug is being evaluated in other malignancies such as high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, mantle cell lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma.4

The primary end point of the expansion portion of the trial was ORR as assessed by an independent review committee. Secondary end points include DOR, complete response (CR) rate, duration of CR, progression-free survival, and time to response. Additional secondary end points include overall survival, time to next therapy, and rate of minimal residual disease negativity.1

Regarding safety, the most common treatment-emergent toxicity is cytokine release syndrome (CRS), occurring in 66.4% of patients, with 1.6% of cases being grade 3 or higher.2

Additional data from the follicular lymphoma cohort of the open-label study are expected to be presented at the upcoming ASH Annual Meeting in December 2023.1


  1. AbbVie announces US Food and Drug Administration (FDA) and European Medicines Agency (EMA) updates for epcoritamab (Epkinly/Tepkinly) for the treatment of relapsed/refractory follicular lymphoma. News release. AbbVie. November 27, 2023. Accessed November 27, 2023. https://news.abbvie.com/2023-11-27-AbbVie-Announces-U-S-Food-and-Drug-Administration-FDA-and-European-Medicines-Agency-EMA-Updates
  2. AbbVie and Genmab announce positive topline results from phase 1/2 EPCORE NHL-1 trial evaluating epcoritamab (DuoBody CD3xCD20) in patients with relapsed/refractory follicular lymphoma (FL). News release. AbbVie. June 27, 2023. Accessed November 27, 2023. https://news.abbvie.com/2023-06-27-AbbVie-and-Genmab-Announce-Positive-Topline-Results-from-Phase-1-2-EPCORE-TM-NHL-1-Trial
  3. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA. May 19, 2023. Accessed November 27, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
  4. First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma (EPCORE NHL-1). ClinicalTrials.gov. Updated August 8, 2023. Accessed November 27, 2023. https://clinicaltrials.gov/study/NCT03625037
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