On 26 June 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.
Efficacy and safety were evaluated in EPCORE NHL-1 (Study GCT3013-01; NCT03625037), an open-label, multi-cohort, multicentre, single-arm study that included 127 patients with relapsed or refractory follicular lymphoma 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 optimisation 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% 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 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 CRS and Immune Effector Cell-Associated Neurotoxicity (ICANS). Warnings and precautions include serious infections and cytopaenias. 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, CRS, COVID-19 infection, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhoea, 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 haemoglobin.
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 III randomised study (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 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 designation.
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EMA recommends extension of therapeutic indications for epcoritamab to patients with relapsed or refractory follicular lymphoma
On 27 June 2024, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product epcoritamab (Tepkinly).
The marketing authorisation holder for this medicinal product is AbbVie Deutschland GmbH & Co. KG.
The CHMP adopted a new indication to include treatment of adults with relapsed or refractory follicular lymphoma.
For information, the full indications for Tepkinly will be as follows (new indication in bold):
Tepkinly as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy.
Tepkinly as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
Detailed recommendations for the use of this product will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report, and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.
Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion.