The FDA has accepted and granted priority review to a biologics license application seeking the apporoval of epcoritamab in patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy.
Jan van de Winkel, PhD
The FDA has accepted and granted priority review to a biologics license application (BLA) seeking the approval of epcoritamab (DuoBody-CD3xCD20) in patients with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy.1
The BLA was based on findings from the pivotal phase 2 EPCORE NHL-1 trial (NCT03625037), in which patients with LBCL who received the investigational bispecific antibody (n = 157) achieved an overall response rate (ORR) of 63% (95% CI, 55%-71%), including a complete response (CR) rate of 39% (95% CI, 31%-47%).2 Three patients experienced stable disease and 24% had disease progression.
Additionally, the median duration of response (DOR) for patients who achieved a CR was not yet reached (NR). The median time to CR was 2.7 months (range, 1.2-11.1). At a median follow-up of 10.7 months (range, 0.3-17.9), the overall median DOR was 12.0 months (range, 0+ to 15.5+). The median time to response (TTR) was 1.4 months (range, 1.0-8.4).
The median overall survival (OS) with epcoritamab was NR, and the 6- 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 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%).
The FDA has set a target action date of May 21, 2023, under the Prescription Drug User Fee Act.
“We are pleased that the BLA for epcoritamab has been accepted for priority review by the FDA, accelerating the pathway for approval and bringing us one step closer to potentially delivering a novel treatment option to [patients with] relapsed and refractory LBCL who are in need of additional treatment options,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in a press release. “Together with our partner, AbbVie, we recognize the unmet need for safe, effective and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population.”
EPCORE NHL-1 enrolled patients with relapsed or refractory, CD20-positive mature B-cell neoplasms who received at least 2 previous lines of therapy, including at least 1 anti-CD20 monoclonal antibody. Patients were permitted to have received prior CAR T-cell therapy, and they needed to have an ECOG performance status of 0 to 2.
The LBCL cohort included patients with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), and follicular lymphoma grade 3B (FL Gr3B).
Enrolled patients received 48 mg of subcutaneous epcoritamab once per week during cycles 1 to 3, then twice weekly in cycles 4 to 9, and 4 times per week thereafter. Treatment continued until disease progression or unacceptable toxicity.
ORR per independent review committee served as the trial’s primary end point. Secondary end points included DOR, TTR, OS, CR rate, PFS, and safety/tolerability.
Within the LBCL cohort, the median age was 64 years (range, 20-83). Additionally, 89% of patients had DLBCL, including 70% with 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% received at least 3 previous treatments. Furthermore, 61% of patients had primary refractory disease, with 83% of patients being refractory to their last systemic therapy received. Thirty-nine percent of patients previously received CAR T-cell therapy, 75% of whom 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 reasons for discontinuation were disease progression (53%), toxicity (7%), allogeneic stem cell transplant (4%), patient withdrawal (3%), or unspecified (1%).
Regarding safety, most toxicities were found to be low grade and presented in the first 3 treatment cycles. The most common adverse effects of any grade included 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.