FDA Approval Sought for Epcoritamab as R/R LBCL Treatment

Positive efficacy and safety results from the phase 3 EPCORE™ NHL-1 trial have lead to an FDA application for approval of epcoritamab to treat relapsed or refractory large B-cell lymphoma.

A biologics license application (BLA) has been submitted to the FDA, seeking approval of the investigational bispecific antibody, subcutaneous epcoritamab (DuoBody®-CD3xCD20), for the treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy.1

The BLA submission is supported by findings from the randomized, multicenter, open-label, phase 2 EPCORE™ NHL-1 trial (NCT03625037). In the study, epcoritamab achieved deep and durable response in the patient population.

“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,” said Jan van de Winkel, PhD, chief executive officer of Genmab, 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 confirmed overall response rate (ORR) observed with epcoritamab in EPCORE™ NHL-1 in patients with LBCL treated with at least 3 prior lines of therapy was 63% with a complete response (CR) rate of 39% in the overall population. Investigator assessed response in patients who were naïve to chimeric antigen receptor (CAR) T cells and those who were refractory to CAR T cells. In the CAR T-naïve population, the ORR was 60% with a 42% CR rate. In patients who failed on CAR T-cell therapy, the ORR with epcoritamab was 54% with a CR rate of 34%. At a median follow-up of 10.7 months, epcoritamab achieved a median duration of response (DOR) of 12 months.2

In terms of safety, the most common any-grade treatment-emergent adverse events (TEAEs) included cytokine release syndrome (CRS; 49.7%), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), and diarrhea (20.4%). TEAEs of any-grade occurred in 20% of patients. The grade 3 or 4 TEAEs most commonly observed were neutropenia (14.6%), anemia (10.2%), neutrophil count decreased (6.4%), and thrombocytopenia (5.7%). Grade 3/4 TEAEs occurred in 5% of patients in the study. There were also cases of grade 3 CRS in 2.5% of patients.

EPCORE NHL-1 is actively recruiting patients with relapsed/refractory LBCL who are heavily pretreated and have an ECOG performance status of 0-2, detectable disease on PET scan. adequate liver and renal function, and a life expectancy of at least 2 months. Patients enrolled will be assessed for the primary end point of overall survival, and secondary efficacy end points including, progression-free survival, ORR, complete response rate, duration of response, time to response, rate and duration of minimal residual disease (MRD) negative status, time to next anti-lymphoma therapy, and anti-epcoritamab antibody response.3

Secondary safety end points being explored in the study include the incidence and severity of AEs, the incidence and severity of changes in laboratory values, incidence of dose delays, and health-related quality of life.


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 A/S. October 28, 2022. Accessed October 28, 2022. https://bwnews.pr/3fawTLf

2. Genmab announces late-breaking phase 2 trial results of investigational epcoritamab (DuoBody®-CD3xCD20) in relapsed/refractory large b-cell lymphoma (LBCL) patients presented at European Hematology Association (EHA) Presidential Symposium. Genmab A/S. June 11, 2022. Accessed October 28, 2022. https://bit.ly/3gRxVMx

3. A phase 3 trial of epcoritamab vs investigator's choice chemotherapy in r/r DLBCL (EPCORE™DLBCL-1), ClinicalTrials.gov. Updated September 16, 2022. Accessed October 28, 2022. https://clinicaltrials.gov/ct2/show/NCT04628494?term=epcoritamab&draw=2