Epcoritamab Approaches EU Approval for Relapsed/Refractory DLBCL

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The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending conditional marketing authorization to epcoritamab-bysp (Tepkinly) monotherapy for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after 2 or more lines of systemic therapy.¹

The final European Commission decision on the indication for epcoritamab is expected later in 2023.

The positive opinion is supported by data from the phase 1/2 EPCORE NHL-1 trial (NCT03625037), which showed that at a median follow-up of 10.7 months, patients with CD20-positive LBCL (n = 157) achieved an overall response rate of 63.1% (95% CI, 55.0%-70.6%), including a complete response (CR) rate of 38.9% (95% CI, 31.2%-46.9%). The median duration of response (DOR) was 12.0 months for all responders, and the median DOR was not reached in patients who achieved a CR.²

“Today’s CHMP opinion is an important step forward in our mission to bringing innovative, readily available medicines like epcoritamab to patients in Europe who are in need of alternative treatment options for relapsed or refractory DLBCL,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in a news release.¹ “We look forward to continuing our work with AbbVie to develop epcoritamab as a potential core therapy across B-cell malignancies.”

In May 2023, the FDA approved epcoritamab for the treatment of adult patients with relapsed/refractory DLBCL not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBCL), after 2 or more lines of systemic therapies.³ That regulatory decision was also supported by data from EPCORE NHL-1.

The open-label, multicenter phase 1/2 trial is evaluating the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive or refractory CD20-positive mature B-cell non-Hodgkin lymphoma, including those with DLBCL.

In the dose-expansion portion of the study, patients were required to have documented CD20-positive mature B cell neoplasm or CD20-positive mantle cell lymphoma (MCL). This included patients with de novo or transformed DLBCL, primary mediastinal large B-cell lymphoma, grade 3B follicular lymphoma, histologically confirmed follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma. Those with MCL who received a prior BTK inhibitor or were intolerant to a BTK inhibitor were also permitted to enroll.

Patients were required to have received at least 2 prior therapies, including an anti-CD20 monoclonal antibody containing chemotherapy combination regimen, and they need to have either failed or been ineligible for prior autologous hematopoietic stem cell transplant.

Patients were excluded if they had primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening, or a known past or current malignancy other than inclusion diagnosis.

Subcutaneous epcoritamab was administered at 48 mg once weekly during cycles 1 to 3, then once every 2 weeks in cycles 4 to 9, and then one every 4 weeks in cycle 10 and beyond. During cycle 1, a step-up dose of 0.16 mg of subcutaneous epcoritamab was given on day 1, followed by an intermediate dose of 0.8 mg on day 8, then the full 48-mg dose on day 15 and thereafter. Treatment continued until disease progression or unacceptable toxicity.²

ORR per independent review committee served as the trial’s primary end point. Key secondary end points included DOR, CR rate, time to response, overall survival, progression-free survival, and safety/tolerability.

Regarding safety, the most common treatment-emergent adverse effects included were cytokine release syndrome (any-grade, 49.7%; grade 1/2, 47.1%; grade 3, 2.5%), pyrexia (any-grade, 23.6%), and fatigue (any-grade, 22.9%). Notably, immune effector cell–associated neurotoxicity syndrome was reported in 6.4% of patients, including 1 patient who experienced a fatal event.

References

1. Genmab announces AbbVie receives positive CHMP opinion for epcoritamab (Tepkinly) for the treatment of adults with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). News release. Genmab. July 21, 2023. Accessed July 21, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-abbvie-receives-positive-chmp-opinion
2. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41(12):2238-2247. doi:10.1200/JCO.22.01725
3. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA. May 19, 2023. Accessed July 21, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
4. First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma (EPCORE NHL-1). ClinicalTrials.gov. Updated June 28, 2023. Accessed July 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03625037