Epcoritamab-bysp Granted Accelerated Approval for Relapsed or Refractory Follicular Lymphoma

Matthew Hadfield, DO.

The FDA has granted accelerated approval to epcoritamab-bysp (Epkinly™, Genmab US, Inc.) for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. Epcoritamab-bysp is a bispecific CD20-directed CD3 T-cell engager.

Why it matters: “The accelerated FDA approval of epcoritamab is notable for multiple reasons,” commented Matthew Hadfield, DO, Oncology Data Advisor board member, of Brown University. “It is the first approved T-cell bispecific–engaging therapy administered subcutaneously for patients with relapsed/refractory follicular lymphoma providing durable responses in a pretreated population.”

What they studied: Efficacy was assessed in the phase 1/2, single-arm, open-label, multicohort trial which enrolled 127 patients with relapsed or refractory FL after at least two lines of systemic therapy. Efficacy and safety were based on the 127 patients who received a two step-up dosing regimen; a separate cohort of 86 patients for dose optimization was evaluated with the recommended three step-up dosing schedule for cytokine release syndrome (CRS) mitigation.

The primary efficacy outcomes measured were overall response rate and duration of response, as determined by an Independent Review Committee using the Lugano 2014 criteria.

What they found: In the overall primary efficacy population of 127 patients, the overall response rate was 82% with 60% complete responses. Of those who responded, the estimated median duration of response was not reached after an estimated median follow-up of 14.8 months. The estimated 12-month duration of response was 68.4%.

For patients in the separate cohort of 86 patients studying the three step-up dosage schedule, efficacy was similar.

Adverse events: The most common adverse events experienced in ≥20% of patients receiving epcoritamab-bysp 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 to 4 laboratory abnormalities experienced in ≥10% of patients receiving epcoritamab-bysp were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and decreased hemoglobin.

A Boxed Warning for serious or fatal CRS and immune effector cell–associated neurotoxicity (ICANS) is included in the prescribing information. Included in the warnings and precautions are serious infections and cytopenias. ICANS occurred in 6% and serious infections in 40% of those receiving epcoritamab. Among 86 patients with relapsed or refractory FL who received the recommended three-step dosage regimen, CRS occurred in 49%; all events were grades 1 (45%) or 2 (9%). 

Conclusion: “The subcutaneous formulation will reduce time toxicity for patients given the much quicker administration time compared to other therapies, as well as decreased burden to infusion staff,” concluded Dr. Hadfield. “The results of the EPCORE-NHL 1 trial and the subsequent approval are a big advancement for patients with this disease, and it is poised to have big implications for all B-cell malignancies.”

What’s next: To establish the clinical benefit of epcoritamab-bysp, a phase 3 randomized trial (NCT05409066) is ongoing to evaluate rituximab and lenalidomide alone or in combination with epcoritamab-bysp in patients with relapsed or refractory FL.

Instructions: The recommended regimen of epcoritamab-bysp consists of subcutaneous administration in 28-day cycles until disease progression or unacceptable toxicity. The recommended dosage of epcoritamab-bysp is a three step-up dosage schedule in Cycle 1 at 0.16 mg on Day 1, 0.8 mg on Day 8, 3.0 mg on Day 15, and 48.0 mg on Day 22; Cycle 2 and 3 at 48.0 mg on Days 1, 8, 15, and 22; Cycles 4 to 9 at 48 mg on Days 1 and 15; and Cycle 10 and beyond at 48 mg on Day 1.

For More Information

Linton KM, Vitolo U, Jurczak W, et al (2024). Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol, S2352-3026(24)00166-2. DOI:10.1016/S2352-3026(24)00166-2

Epkinly™ (epcoritamab-bsyp) prescribing information (2024). Genmab US, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761324s003lbl.pdf

Clinicaltrials.gov (2024). First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma (EPCORE™ NHL-1). NLM identifier: NCT03625037.

US Food and Drug Administration (2024). FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma

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