FDA Approves Epcoritamab for Treatment of Relapsed, Refractory Follicular Lymphoma

The FDA approved epcoritamab-bysp (Epkinly; Genamb, AbbVie) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after 2 or more lines of systemic therapy.¹

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The approval marks the first and only T-cell engaging bispecific antibody administered subcutaneously to treat this patient population, according to a news release. In February 2024, the FDA granted priority review for this indication. Continued approval for the indication may be dependent on verification and description of clinical benefit in a confirmatory clinical trial.^1,2

“Patients with [R/R FL] face significant treatment challenges, especially in third-line settings where there is currently no clear standard of care treatment,” Jeff Sharman, MD, disease chair for hematology research at the Sarah Cannon Research Institute at Willamette Valley Cancer Institute in Eugene, Oregon, said in the news release. “This approval and the durable responses observed in the [FL] cohort of the EPCORE NHL-1 clinical trial, which reflected a real-world patient population, including patients with difficult-to-treat follicular lymphoma, demonstrate the potential of [epcoritamab-bysp] for patients who face limited therapeutic options post-relapse.”¹

The results were based on the phase 1/2 EPCORE NHL-1 study, demonstrating clinically meaningful treatment responses in this patient population. The results showed a high overall response rate (ORR) of 82% and compete responses (CR) of 63%, which were previously presented at the Annual Meeting and Exposition of the American Society of Hematology in December 2023.²

The trial was split into 3 parts: a phase 1 dose escalation, a phase 2a expansion, and a phase 2a dose optimization. Investigators included individuals with relapsed, progressive, or refractory CD20-positive mature B-cell non-Hodgkin lymphoma, which included 127 with FL. The primary end point was ORR, and secondary end points included duration of response CR, duration of complete response, progression-free survival, and time to response.²

The median follow-up time was 17.4 months, and a median time to response was 1.4 months, with median CR in 1.5 months. For individuals who were refractory, the ORR and CR were generally consistent with the overall study population. According to the results, at the 12- and 18-month marks, approximately 85% and 74% of patients who experienced CR and remained responsive to the treatment.²

There were no new safety signals identified, with the most common treatment emergent adverse event (AE) being cytokine release syndrome and additional AEs including injection-site reactions, COVID-19, fatigue, neutropenia, diarrhea, and pyrexia.²

“With this approval, patients whose [FL] has relapsed or is refractory to at least 2 or more lines of systemic therapy, now have the option to be treated with epcoritamab-bysp, which has demonstrated durable responses without mandatory hospitalization using a 3 step-up dosage regimen in this patient population in clinical trials,” Jan van de Winkel, PhD, CEO of Genmab, said in the news release. “In just over a year, [epcoritamab-bysp] has received a second indication in the [United States], making it the first and only bispecific antibody approved to treat patients with diffuse large B-cell lymphoma and follicular lymphoma after 2 or more lines of systemic therapy. The approved indications, along with the ongoing clinical development program, underscore the potential of epcoritamab to become a core therapy across B-cell malignancies.”¹

In May 2023, the FDA also approved epcoritamab-bysp as the first and only T-cell engaging bispecific antibody for the treatment of adult patients with R/R diffuse large B-cell lymphoma. Including from indolent lymphoma and high-grade B-cell lymphoma after 2 or more lines of systemic therapies.³

References

1. Epkinly (epcoritamab-bysp) Approved by U.S. FDA for Patients with Relapsed or Refractory (R/R) Follicular Lymphoma (FL). News release. Genmab. June 27, 2024. Accessed June 27, 2024. https://ir.genmab.com/news-releases/news-release-details/epkinlyr-epcoritamab-bysp-approved-us-fda-patients-relapsed-or

2. Gallagher A. FDA Grants Priority Review to Epcoritamab-bysp for Relapsed or Refractory Follicular Lymphoma. Pharmacy Times. February 28, 2024. June 27, 2024. https://www.pharmacytimes.com/view/fda-grants-priority-review-to-epcoritamab-bysp-for-relapsed-or-refractory-follicular-lymphoma

3. Antrim A. FDA Approves Epcoritamab-bysp for Relapsed, Refractory Diffuse Large B-Cell Lymphoma. Pharmacy Times. May 19, 2023. Accessed June 27, 2024. https://www.pharmacytimes.com/view/fda-approves-epcoritamab-bysp-for-relapsed-refractory-diffuse-large-b-cell-lymphoma