On June 26, 2024, 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 (FL) after two or more lines of systemic therapy.

FDA update

Efficacy and safety were evaluated in EPCORE NHL-1 (Study GCT3013-01; NCT03625037), an open-label, multicohort, multicenter, single-arm trial that included 127 patients with relapsed or refractory FL after 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 (CRS) mitigation.

The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by an independent review committee using the Lugano 2014 criteria. In the 127 patients in the primary efficacy population, the ORR was 82% (95% 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 DOR was not reached (95% CI = 13.7, not reached). The 12-month Kaplan-Meier estimate for DOR was 68.4% (95% CI = 57.6%, 77.0%). Efficacy was similar in the 86 patients who received the 3 step-up dosage schedule.

The prescribing information includes a boxed warning for serious or fatal CRS and immune effector cell–associated neurotoxicity (ICANS). Warnings and precautions include serious infections and cytopenias. ICANS occurred in 6% of patients and serious infections in 40%. Among 86 patients with relapsed or refractory FL who received the recommended three step-up dosage regimen, CRS occurred in 49%; all events were grades 1 (45%) or 2 (9%).

The most common adverse reactions reported in at least 20% of patients were injection site reactions, CRS, COVID-19 infection, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, pyrexia, cough, and headache. The most common grade 3 or 4 laboratory abnormalities reported in at least 10% of patients were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and decreased hemoglobin.

The recommended regimen consists of epcoritamab-bysp administered subcutaneously in 28-day cycles until patients experience disease progression or unacceptable toxicity. The recommended dose is a three step-up 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). The full prescribing information for epcoritamab-bysp will be posted on Drugs@FDA.

FDA approved the application under the accelerated approval pathway. To verify the clinical benefit of epcoritamab-bysp, a phase III randomized trial (NCT05409066) is evaluating rituximab and lenalidomide alone or in combination with epcoritamab-bysp in patients with relapsed or refractory FL. The trial is ongoing and close to fully enrolled (95%).

The applicant used the Assessment Aid to facilitate the FDA’s review. FDA granted the application priority review and breakthrough designation. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics and ONS’s Drug Development Terminology Huddle Card.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.