U.S. flag An official website of the United States government
  1. Home
  2. Drugs
  3. Development & Approval Process | Drugs
  4. Drug Approvals and Databases
  5. Resources for Information | Approved Drugs
  6. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma
  1. Resources for Information | Approved Drugs

FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma

On June 26, 2024, the Food and Drug Administration 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 (FL) after two or more lines of systemic therapy.

Full prescribing information for Epkinly will be posted on Drugs@FDA.

Efficacy and safety were evaluated in EPCORE NHL-1 (Study GCT3013-01; NCT03625037), an open-label, multi-cohort, multicenter, single-arm trial that included 127 patients with relapsed or refractory FL after at least 2 lines of systemic therapy. The primary efficacy and safety were based on 127 patients who received a 2 step-up dosing regimen. A separate dose optimization cohort of 86 patients evaluated the recommended 3-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), 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 (NR) (95% CI: 13.7, NR). 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 cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity (ICANS). Warnings and Precautions include serious infections and cytopenias. ICANS occurred in 6.0%, and serious infections in 40%. Among 86 patients with relapsed or refractory follicular lymphoma who received the recommended 3-step dosage regimen, CRS occurred in 49%, all events were grades 1 (45%) or 2 (9%).

The most common adverse reactions (≥20%) 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 (≥10%) 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 disease progression or unacceptable toxicity. The recommended dose is a 3 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-bysp, a Phase 3 randomized trial (NCT05409066) is ongoing and close to fully enrolled (95%), which is evaluating rituximab and lenalidomide alone or in combination with epcoritamab-bysp in patients with relapsed or refractory FL.

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 designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X @FDAOncology.

Back to Top