FDA Approval Sought for Subcutaneous Epcoritamab for Relapsed/Refractory LBCL

Genmab A/S shared plans to submit a biologics license application to the FDA seeking the approval of subcutaneous epcoritamab for the treatment of patients with relapsed or refractory large B-cell lymphoma in the second half of 2022.

Genmab A/S shared plans to submit a biologics license application to the FDA seeking the approval of subcutaneous epcoritamab for the treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) in the second half of 2022.1

The application is supported by findings from a LBCL cohort of the phase 2 EPCORE NHL-1 trial (NCT03625037), in which the first-in-class T-cell–engaging bispecific antibody elicited an overall response rate (ORR) of 63% (95% CI, 55%-71%) in this population (n = 157), which comprised a complete response (CR) rate of 39% (95% CI, 31%-47%).2 A total of 3 patients achieved stable disease and 24% experienced disease progression.

Moreover, the median duration of response (DOR) for those who experienced a CR with the bispecific antibody was not yet reached. The median time to CR was 2.7 months (range, 1.2-11.1). At a median follow-up of time of 10.7 months (range, 0.3-17.9), the overall median DOR was 12.0 months (range, 0+ to 15.5+), and the median time to response (TTR) was 1.4 months (range, 1.0-8.4).

The median overall survival (OS) with epcoritamab had not yet been reached (NR). The 6-month OS rate was 70.6% (95% CI, 62.7%-77.2%) with the agent in this cohort, and the 12-month OS rate was 56.9% (95% CI, 47.3%-65.4%). The median progression-free survival (PFS) in those who achieved a CR was not yet reached; 89% of complete responders remained in 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%).

“Relapsed or refractory LBCL is often difficult to treat, and patients are in need of novel therapies that are effective, tolerable, and accessible,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in a press release. “The results from the EPCORE NHL-1 trial, and other clinical trials evaluating epcoritamab in a variety of patients and treatment settings, have demonstrated that epcoritamab has the potential to offer people living with LBCL a new therapeutic advance with a manageable safety profile.”

Patients with relapsed or refractory, CD20-positive mature B-cell neoplasms were enrolled to EPCORE NHL-1. Patients were required to have an ECOG performance of 0 to 2, and to have undergone at least 2 previous lines of therapy, including at least 1 anti-CD20 monoclonal antibody. Patients were allowed to have received prior treatment with a CAR T-cell therapy.

Study participants were given subcutaneous epcoritamab at a weekly dose of 48 mg during cycles 1 through 3, biweekly during cycles 4 to 9, and 4 times per week during cycle 10 and beyond. Treatment was administered until disease progression or intolerable toxicity.

Those specifically enrolled to the LBCL cohort had diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), and follicular lymphoma grade 3B (FL Gr3B).

The primary end point of the trial was ORR per independent review committee, and secondary end points comprised DOR, TTR, OS, CR rate, PFS, and safety/tolerability.

The median patient age in the LBCL cohort was 64 years (range, 20-83). Eighty-nine percent of patients had DLBCL, 70% of whom had de novo DLBCL. Moreover, 9 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), with more than half of patients (71%) having received at least 3 previous treatments. Sixty-one percent of patients had primary refractory disease, with 83% of patients being refractory to their last systemic therapy received. Moreover, 39% of patients previously received CAR T-cell therapy, with 75% having 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%).

Additional findings presented during the 2022 EHA Congress indicated that responses achieved with epcoritamab were consistent across the subsets of patients examined. Irrespective of age, disease histology, exposure to CAR T-cell therapy, or number of prior treatments, patients achieved an ORR of at least 46% with the bispecific antibody.

Those who never received CAR T-cell therapy (n = 96%) experienced an ORR of 69% with epcoritamab, with a 27% CR rate. The ORRs induced in those who were 75 years or older (n = 29) or who had transformed DLBCL (n = 40) were 72% and 68%, respectively.

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


  1. Genmab to submit biologics license application to US Food and Drug Administration for epcoritamab (DuoBody-CD3xCD20) for the treatment of relapsed/refractory large B-cell lymphoma large B-cell lymphoma (LBCL). News release. Genmab A/S. June 30, 2022. Accessed June 30, 2022. https://bit.ly/3I8MqoF
  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