FDA/European Approval Sought for Epcoritamab in Relapsed/Refractory LBCL/DLBCL

A biologics license application has been submitted to the FDA seeking the approval of subcutaneous epcoritamab for the treatment of patients with relapsed/refractory large B-cell lymphoma or diffuse large B-cell lymphoma after 2 or more lines of systemic therapy.

A biologics license application (BLA) has been submitted to the FDA seeking the approval of subcutaneous epcoritamab for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) or diffuse large B-cell lymphoma (DLBCL) after 2 or more lines of systemic therapy.1

The European Medicines Agency (EMA) has also validated a marketing authorization application (MAA) seeking the approval of epcoritamab in patients with relapsed or refractory DLBCL following 2 or more lines of systemic treatment.

The BLA and MAA were based on data from the phase 2 EPCORE NHL-1 trial (NCT03625037), which evaluated the safety and preliminary efficacy of the agent in patients with relapsed, progressive or refractory CD20-positive, mature B-cell non-Hodgkin lymphoma (B-NHL), including DLBCL.

Data presented at the 2022 EHA Congress showed that patients with LBCL who were treated with epcoritamab (n = 157) experienced an overall response rate (ORR) of 63% (95% CI, 55%-71%), including a complete response (CR) rate of 39% (95% CI, 31%-47%).2 Additionally, 3% of patients had stable disease and 24% had progressive disease.

Notably, the median duration of response (DOR) for patients who experienced a CR was not reached (NR). The median time to CR was 2.7 months (range, 1.2-11.1), and the overall median DOR was 12.0 months (range, 0+ to 15.5+). Moreover, the median time to response was 1.4 months (range, 1.0-8.4).

The median overall survival (OS) was NR, and the 6-month and 12-month OS rates were 70.6% (95% CI, 62.7%-77.2%) and 56.9% (95% CI, 47.3%-65.4%), respectively. The median progression-free survival (PFS) in those who achieved a CR was NR, and 89% of complete responders maintained a CR at 9 months. The overall median PFS was 4.4 months (95% CI, 2.0-7.9), and the overall 6-month PFS rate was 43.9% (95% CI, 35.7%-51.7%).

“Even with existing therapies to treat these lymphomas, there is a significant medical need for alternative and accessible treatment options for patients who are unable to tolerate current treatments or whose treatments have failed,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in a press release. “Together with our partner AbbVie, we believe epcoritamab has the potential to become a core therapy for patients with B-cell malignancies, and the submission of these regulatory applications to the FDA and EMA is an important step in potentially bringing epcoritamab to people living with relapsed/refractory B-cell lymphomas.”

The open-label, multicenter EPCORE NHL-1 trial enrolled patients with relapsed/refractory, CD20-positive mature B-cell neoplasms who received at least 2 prior lines of antineoplastic therapy, including at least 1 anti-CD20 monoclonal antibody. The LBCL cohort included patients with DLBCL, high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), or follicular lymphoma grade 3B (FL Gr3B).

Patients were required to have an ECOG performance status of 0 to 2, and prior CAR T-cell therapy was permitted.

Enrolled patients were treated with 48 mg of subcutaneous epcoritamab once per week in cycles 1 to 3, once every 2 weeks in cycles 4 to 9, and once every 4 weeks thereafter. Treatment continued until progressive disease or unacceptable toxicity.

ORR per independent review committee served as the trial’s primary end point. Secondary end points were comprised of DOR, time to response, PFS, OS, CR rate, and safety.

Those enrolled in the LBCL cohort had a median age of 64 years (range, 20-83). Eighty-nine percent of patients had DLBCL, 70% of whom had de novo DLBCL. Nine patients had HGBCL, 4 had PMBCL, and 5 had FL Gr3B. Forty-seven percent of the patients had an ECOG performance of 0.

The median number of prior lines of therapy received was 3 (range, 2-11), and 71% of patients received at least 3 previous treatments. Additionally, 61% of patients had primary refractory disease, and 83% of patients were refractory to their last systemic therapy. Thirty-nine percent of patients received prior CAR T-cell therapy, and 75% of those progressed within 6 months of treatment.

At a data cutoff of January 31, 2022, 32% of patients were still receiving treatment with epcoritamab, and 68% had discontinued. The most common reason for discontinuation was disease progression (53%), followed by toxicity (7%), allogeneic stem cell transplant (4%), patient withdrawal (3%), or another unspecified reason (1%).

Regarding safety, most toxicities were low grade and presented in the first 3 treatment cycles. The most frequently experienced any-grade adverse effects included cytokine release syndrome (49.6%), neutropenia (28%), pyrexia (23.5%), and fatigue (22.9%). Ten patients experienced immune effector cell–associated neurotoxicity syndrome of any grade, including 9 cases that were grade 1 or 2 and resolved; 1 case was grade 5 in severity.


  1. Genmab announces submissions of regulatory applications for epcoritamab (DuoBody-CD3xCD20) for the treatment of relapsed/refractory large B-cell lymphoma (LBCL) and diffuse large B-cell lymphoma (DLBCL). News release. Genmab. October 28, 2022. Accessed October 28, 2022. https://bit.ly/3zrwvic
  2. Thieblemont C, Phillips T, Ghesquieres H, et al. Primary results of subcutaneous epcoritamab dose expansion in patients with relapsed or refractory large B-cell lymphoma: a phase 2 study. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract LB2364 https://bit.ly/3fnyFbH
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