Epcoritamab Earns FDA BTD in Relapsed/Refractory Follicular Lymphoma

Supporting data for the breakthrough therapy designation came from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).

The FDA has granted breakthrough therapy designation to epcoritamab-bysp (Epkinly) as a treatment for adult patients with relapsed/refractory follicular lymphoma previously treated with at least 2 lines of therapy, according to a press release from AbbVie.¹

A Type II application for epcoritamab (Tepkinly) for the same indication has also been validated by the European Medicines Agency.

Supporting data for the breakthrough therapy designation came from the phase 1/2 EPCORE NHL-1 trial (NCT03625037). Previously published findings from the trial’s follicular lymphoma cohort highlighted an overall response rate of 82% based on independent review committee assessment.² The median duration of response (DOR) was not reached among those who had a response.

Investigators observed any-grade cytokine release syndrome (CRS) in 66.4% of patients treated with epcoritamab. Grade 3 or higher CRS affected 1.6% of patients. Overall, treatment with the experimental agent produced no new safety signals.

Updated findings from the EPCORE NHL-1 trial are set to be presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

“The FDA [breakthrough therapy designation] and validated European application are an important step in our commitment to improving the lives of patients with relapsed/refractory follicular lymphoma, a complex blood cancer with limited treatment options,” Mariana Cota Stirner, MD, PhD, vice president, therapeutic area head for hematology at AbbVie, said in the press release.¹ “Together with Genmab, we are continuing to investigate epcoritamab as a potential core therapy for multiple B-cell malignancies, including diffuse large B-cell lymphoma and now follicular lymphoma.”

Investigators of the open-label, multi-center EPCORE NHL-1 trial assessed subcutaneous epcoritamab among adult patients with relapsed/refractory CD20-positive mature B-cell non-Hodgkin lymphoma, which included those with follicular lymphoma. The study consisted of 3 portions: a phase 1 first-in-human portion, a phase 2a dose expansion portion, and a phase 2a dose optimization stage.

The primary end point of the trial’s expansion portion was ORR as determined by an independent review committee. Secondary end points included DOR, duration of complete response, progression-free survival, time to response, overall survival, time to next therapy, and minimal residual disease negativity.

Patients 18 years and older with a documented CD20-positive mature B-cell neoplasm including but not limited to follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or primary mediastinal large B-cell lymphoma were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of no higher than 2; measurable disease by CT, MRI, or CT-PET scan; and acceptable liver and renal function.

Patients with primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had clinically significant cardiovascular disease, received any prior therapy with an investigational agent targeting CD3 and CD20, had autoimmune disease or other diseases resulting in permanent immunosuppression, active hepatitis B or hepatitis C, or a contraindication to all agents that lower uric acid.

References

1. AbbVie announces U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) updates for epcoritamab (EPKINLY®/TEPKINLY®) for the treatment of relapsed/refractory follicular lymphoma. News release. AbbVie. November 27, 2023. Accessed November 28, 2023. https://shorturl.at/bxBY3
2. AbbVie and Genmab announce positive topline results from phase 1/2 EPCORE™ NHL-1 trial evaluating epcoritamab (DuoBody®-CD3xCD20) in patients with relapsed/refractory follicular lymphoma (FL). News release. Abbvie and Genmab. June 27, 2023. Accessed November 28, 2023. https://shorturl.at/eBHOZ