FDA Grants Priority Review to sBLA of Epcoritamab in Relapsed/Refractory Follicular Lymphoma

The FDA has granted priority review to the supplemental biologics license application (sBLA) seeking the approval of epcoritamab-bysp (Epkinly) for the treatment of adult patients with relapsed/refractory follicular lymphoma after 2 or more lines of systemic therapy.¹

The sBLA is supported by data from the phase 1/2 EPCORE NHL-1 trial (NCT03625037), which were presented at the 2023 ASH Annual Meeting. Findings demonstrated that at a median follow-up of 17.4 months, patients treated with subcutaneous epcoritamab (n = 128) experienced an overall response rate (ORR) of 82% and a complete response (CR) rate of 63%. Notably, the estimated rates of patients who experienced a CR and remained in response at 12 and 18 months were 85% and 74%, respectively.²

“While treatment for patients with relapsed and refractory follicular lymphoma has progressed, there remains an urgent need for new treatment options, particularly for patients who are considered difficult to treat due to relapse following standard therapies and other poor prognostic factors,” Jan van de Winkel, PhD, CEO of Genmab, stated in a press release.¹ “The acceptance of the epcoritamab application for priority review marks an important milestone toward potentially providing a new treatment option to patients affected by relapsed/refractory follicular lymphoma. Together with AbbVie, we look forward to working with the FDA during the review and remain committed to developing epcoritamab as a potential future core therapy for B-cell malignancies.”

The open-label, multicenter EPCORE NHL-1 trial enrolled patients with relapsed, progressive, or refractory, CD20-positive, mature B-cell non-Hodgkin lymphoma, including follicular lymphoma. The study consisted of 3 parts: dose escalation, expansion, and optimization.

Key inclusion criteria for escalation included relapsed and/or refractory disease after treatment with an anti-CD20 monoclonal antibody and/or relapsed after autologous stem cell transplant; an ECOG performance status 0 to 2; measurable disease; and acceptable renal and liver function. During the dose-expansion and -optimization parts, at least 2 prior therapies, including an anti-CD20 monoclonal antibody containing chemotherapy combination regimen, were required.³

In all parts, patients were excluded if they had primary central nervous system (CNS) lymphoma or CNS involvement at screening; received any prior therapy with an investigational bispecific antibody targeting CD3 and CD20; or had prior treatment with CAR T-cell therapy within 30 days prior to first epcoritamab administration.

The primary end points during dose escalation included dose-limiting toxicities and adverse effects (AEs). For patients with follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma, the rates of grade 2 or higher cytokine release syndrome (CRS) and all-grade CRS events served as a primary end point during the dose optimization phase.

Additional data for patients with follicular lymphoma showed that the median time to response and CR was 1.4 months and 1.5 months, respectively. For patients who achieved a CR, the median progression-free survival, duration of response, duration of CR, minimal residual disease (MRD) negativity, and overall survival were not reached. The MRD negativity rate for the overall cohort was 67%.²

The ORR and CR rates in prespecified subgroups were generally consistent with the overall patient population. Those who were high risk and refractory to both anti-CD20 therapy and an alkylating agent experienced an ORR of 76% and a CR rate of 56%. Those who were refractory to last prior treatment had an ORR and CR rate of 74% and 51%, respectively. The ORR was 80% and the CR rate was 61% for patients whose disease progressed within 2 years of first-line immunochemotherapy.

Safety findings were consistent with prior epcoritamab clinical trials, and the agent was generally well tolerated. In patients with follicular lymphoma who were treated with an optimized step-up dose regimen (n = 50), the rate of grade 1 CRS was 40%, and the rate of grade 2 CRS was 8%. No incidences of grade 3 or higher CRS or any-grade immune effector cell–associated neurotoxicity syndrome were reported in these patients.

The most common treatment-emergent AEs (TEAEs) were reported in more than 20% of patients in the overall follicular lymphoma cohort included injection-site reaction (57%), COVID-19 (40%), fatigue (30%), neutropenia (29%), diarrhea (27%), and pyrexia (25%). Nineteen percent of patients discontinued treatment due to TEAEs, and 10% of patients (n = 13) experienced grade 5 TEAEs.

References

1. U.S. FDA accepts for priority review the supplemental biologics license application for epcoritamab (Epkinly) for difficult-to-treat relapsed or refractory follicular lymphoma. News release. Genmab and AbbVie. February 27, 2024. Accessed February 27, 2024. https://ir.genmab.com/news-releases/news-release-details/us-fda-accepts-priority-review-supplemental-biologics-license
2. New pivotal data for bispecific antibody epcoritamab (DuoBody CD3xCD20) demonstrates high overall and complete responses in patients with hard-to-treat relapsed/refractory follicular lymphoma (FL). News release. Genmab and AbbVie. December 9, 2023. Accessed February 27, 2024. https://ir.genmab.com/news-releases/news-release-details/new-pivotal-data-bispecific-antibody-epcoritamab-duobodyr
3. First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma (EPCORE NHL-1). ClinicalTrials.gov. Updated February 16, 2024. Accessed February 27, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03625037