FDA Grants Accelerated Approval to Epcoritamab-bysp for Relapsed or Refractory Follicular Lymphoma

On June 26, 2024, the Food and Drug Administration (FDA) granted accelerated approval to epcoritamab-bysp (Epkinly, Genmab US, Inc.), a bispecific CD20-directed CD3 T-cell engager, for adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

The efficacy and safety of epcoritamab-bysp were assessed in the EPCORE NHL-1 (Study GCT3013-01; NCT03625037), an open-label, multicohort, multicenter, single-arm study involving 127 patients with relapsed or refractory follicular lymphoma who had previously received at least two lines of systemic therapy. The primary efficacy and safety analysis focused on the subset of 127 patients who underwent a two-step dosing regimen. An additional dose optimization cohort of 86 patients was utilized to evaluate a recommended three-step dosing schedule for mitigating cytokine release syndrome (CRS).

Key efficacy endpoints included the overall response rate (ORR) and duration of response (DoR) as assessed by an Independent Review Committee using the Lugano 2014 criteria. Among the 127 patients in the primary efficacy analysis, the ORR was 82% (95% confidence interval [CI] 74.1, 88.2), with 60% achieving complete responses. The median DoR was not reached (NR) (95% CI 13.7, NR) at an estimated median follow-up duration of 14.8 months for responders. The 12-month Kaplan-Meier estimate for DoR was 68.4% (95% CI 57.6%, 77.0%). Similar efficacy outcomes were observed in the 86 patients who followed the three-step dosing schedule.

The prescribing information for epcoritamab-bysp includes a Boxed Warning regarding serious or fatal CRS and Immune Effector Cell-Associated Neurotoxicity (ICANS). Warnings and precautions address serious infections and cytopenias. ICANS occurred in 6.0% of patients, while serious infections were reported in 40%. Among the 86 patients receiving the recommended three-step dosage regimen, 49% experienced CRS events, with all events classified as grades 1 (45%) or 2 (9%).

Common adverse reactions (≥20%) observed in patients included injection site reactions, CRS, COVID-19 infection, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache. The most frequently reported Grade 3 to 4 laboratory abnormalities (≥10%) included decreased lymphocyte count, neutrophil count, white blood cell count, and hemoglobin.

The recommended dosing regimen for epcoritamab-bysp consists of subcutaneous administration in 28-day cycles until disease progression or unacceptable toxicity. The initial dose is a three-step escalation schedule in Cycle 1 (0.16 mg on Day 1, 0.8 mg on Day 8, 3 mg on Day 15, and 48 mg on Day 22), continued in Cycles 2 and 3 (48 mg on Days 1, 8, 15, and 22), and subsequently in Cycles 4 to 9 (48 mg on Days 1 and 15), and Cycle 10 onwards (48 mg on Day 1).

The FDA approved this application under the accelerated approval pathway. To confirm the clinical benefit of epcoritamab-bysp, a phase III randomized study (NCT05409066) comparing rituximab and lenalidomide alone or in combination with epcoritamab-bysp in relapsed or refractory follicular lymphoma patients is nearing full enrollment (95%).

The assessment of epcoritamab-bysp utilized the Assessment Aid, a voluntary tool from the applicant to assist in the FDA's evaluation process.

This application was granted priority review and breakthrough designation status.

Healthcare professionals are encouraged to report any suspected serious adverse events associated with epcoritamab-bysp or any other medications or devices to the FDA's MedWatch Reporting System.