Topline results from the EPCORE NHL-1 trial showed promising efficacy findings and no new safety signals with epcoritamab in a cohort of 128 patients with relapsed/refractory follicular lymphoma.
In a cohort of patients with relapsed/refractory follicular lymphoma (FL) who received at least 2 prior lines of systemic therapy in the phase 1/2 EPCORE NHL-1 trial (NCT03625037), epcoritamab (DuoBody® CD3xCD20) produced an overall response rate (ORR) of 82%, as confirmed by an independent review committee (IRC), which exceeded the protocol prespecified threshold for efficacy.1
According to topline results from this cohort of 128 adult patients with relapsed/refractory FL, 70.3% were double refractory to an anti-CD20 monoclonal antibody and an alkylating agent, and the observed median duration of response (DOR) was not reached. Additionally, no new safety signals were identified with epcoritamab, and the most common treatment-emergent adverse event was cytokine release syndrome (CRS; 66.4%), with 1.6% of patients having grade >2 CRS.
The optimization part of the trial will continue to evaluate alternative step-up dosing regimens to mitigate the risk of CRS, as findings align with the FDA’s Project Optimus. Based on the results from this cohort, along with the results from the optimization part of the trial, data from EPCORE NHL-1 will be submitted for presentation at an upcoming medical meeting.
“These topline results are encouraging for relapsed or refractory follicular lymphoma patients who are in need of new therapeutic options,” said Jan van de Winkel, PhD, chief executive officer of Genmab, in a press release. “With our partner AbbVie, we are committed to evaluating epcoritamab as a potential core therapy across B-cell malignancies. We look forward to sharing the full results from this study cohort at an upcoming medical congress and discussing the results with global regulatory authorities.”
The open-label, multicenter, phase 1/2 EPCORE NHL-1 trial is evaluating the safety and preliminary efficacy trial of epcoritamab among patients with relapsed/refractory FL.2 The trial is made up of 3 parts, including a phase 1 first-in-human, dose escalation part, a phase 2 expansion part, and an optimization part.
The goal of the dose-escalation part of the trial was to determine the maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of epcoritamab and aimed to establish the safety profile of the agent in patients with relapsed, progressive, or refractory B-cell lymphoma. Then, the expansion part enrolled additional patients with relapsed, progressive, or refractory CD20-positive mature B-cell non-Hodgkin’s lymphoma (B-NHL), including FL who were given epcoritamab at the RP2D to further explore and determine the safety and efficacy of epcoritamab. Further, the dose-optimization part of the trial plans to evaluate alternative priming and intermediate dose regimens of epcoritamab among patients who will be treated at the RP2D.
For the expansion and optimization parts of the study, patients aged 18 years and older were eligible for enrollment if they had a documented CD20-positive mature B-cell neoplasm, relapsed, and had progressive and/or refractory disease after receiving treatment with an anti-CD20 monoclonal antibody, including in combination with chemotherapy and/or relapsed after autologous stem cell rescue. Patients were required to have an ECOG performance status 0,1, or 2, measurable disease by CT, MRI or PET-CT scan, and acceptable renal and liver function.
The primary end point for the expansion part of the trial ORR as assessed by an IRC, and secondary efficacy end points were DOR, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Additional secondary end points included overall survival, time to next therapy, and rate of minimal residual disease negativity.