ASH 2025 | Primary Phase III results from the EPCORE FL-1 trial: epcoritamab plus R2 versus R2 for R/R FL

So this year at ASH, it was really a tremendous honor to represent all my co-authors in sharing the primary analysis of this randomized control phase 3 trial called EPCORE-FL1 that tested epcoritamab with rituximab and lenalidomide versus rituximab and lenalidomide alone for patients with follicular lymphoma after at least one line of systemic therapy. Patients with follicular lymphoma that comes back after one line of therapy are in dire need because most patients relapse and the likelihood of response and the duration of that response tends to shorten and lower with each subsequent line of therapy. So clearly we need treatment regimens with improved efficacy and improved durability of responses. Epcoritamab is already approved as a single agent for relapsed refractory follicular lymphoma, and because there’s no overlapping toxicity and potentially some synergistic activity between epcoritamab and the R-squared component, we decided to combine those two and test them first in a phase 1-2 study, which was called EPCORE NHL-2. In that study, we enrolled over 100 patients and saw very promising efficacy results with a manageable safety profile. And now, in a full-fledged randomized phase three trial testing the triplet versus our R-squared doublet alone in a one-to-one fashion. 

The study enrolled 488 patients, 245 in the experimental arm and 243 in the control arm. Most patients finished treatment. The number of patients who discontinued treatment prematurely due to progression was higher in the R-squared arm versus the epcoritamab R-squared arm. Most of the premature discontinuations were due to progressive disease. 

So the study, as I mentioned, randomized one-to-one patients with relapsed follicular lymphoma, CD20-positive biopsy-proven, receiving at least one line of therapy that must include anti-CD20 antibody and chemotherapy. And patients were mandated to meet at least one treatment criterion per the GELF criteria. The treatment consisted of R-squared administered per the Augment Protocol, and epcoritamab was given weekly for the first three cycles and then every month, and treatment was continued up to 12 cycles, each lasting 28 days. The dual primary endpoints of the study were overall response rate and progression-free survival, both independently assessed. Key secondary endpoints were complete response rate, overall survival, and minimal residual disease assessment. We obviously had a number of secondary endpoints both for safety and efficacy. The study was stratified by geographic region and disease status, and at the time of this analysis, we had a follow-up of 14.8 months.

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