On June 26, the U.S. Food and Drug Administration (FDA) granted accelerated approval to epcoritamab-bysp (Epkinly), a bispecific CD20-directed CD3 T-cell engager, for adult patients with relapsed or refractory follicular lymphoma who have received two or more lines of systemic therapy.
EPCORE NHL-1
Efficacy and safety were evaluated in EPCORE NHL-1 (Study GCT3013-01; ClinicalTrials.gov identifier NCT03625037), an open-label, multicohort, multicenter, single-arm trial that included 127 patients with relapsed or refractory follicular lymphoma who had received at least two lines of systemic therapy. The primary efficacy and safety were based on 127 patients who received a two step-up dosing regimen. A separate dose optimization cohort of 86 patients evaluated the recommended three-step up dosage schedule for cytokine-release syndrome mitigation.
The main efficacy outcome measures were overall response rate and duration of response, determined by an Independent Review Committee using the Lugano 2014 criteria. In the 127 patients in the primary efficacy population, the overall response rate was 82% (95% confidence interval [CI] = 74.1%–88.2%) with 60% achieving complete responses. With an estimated median follow-up of 14.8 months among responders, the estimated median duration of response was not reached (95% CI = 13.7 months to not reached). The 12-month Kaplan-Meier estimate for duration of response was 68.4% (95% CI = 57.6%–77.0%). Efficacy was similar in the 86 patients who received the three step-up dosage schedule.
The most common adverse reactions (occurring in ≥ 20% of patients who received epcoratimab) were injection-site reactions, cytokine-release syndrome, COVID-19 infection, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, pyrexia, cough, and headache. The most common grade 3 to 4 laboratory abnormalities (occurring in ≥ 10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and decreased hemoglobin.
The prescribing information for epcoratimab includes a Boxed Warning for serious or fatal cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS). Warnings and Precautions include serious infections and cytopenias. ICANS occurred in 6.0% of patients, and serious infections occurred in 40%. Among 86 patients with relapsed or refractory follicular lymphoma who received the recommended three-step dosage regimen, cytokine-release syndrome occurred in 49%; all events were grades 1 (45%) or 2 (9%).
The recommended regimen consists of epcoritamab administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity. The recommended dose is a three step-up dosage 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), cycle 2 and 3 (48 mg on days 1, 8, 15, and 22), cycles 4 to 9 (48 mg on days 1 and 15), and cycle 10 and beyond (48 mg on day 1).
This application is approved under the accelerated approval pathway. To verify the clinical benefit of epcoritamab, a phase III randomized trial (NCT05409066) is ongoing and close to fully enrolled (95%). The study is evaluating rituximab and lenalidomide alone or in combination with epcoritamab in patients with relapsed or refractory follicular lymphoma.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review and Breakthrough Therapy designation.
