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

So the study met both its dual primary endpoints. Epcoritamab R-squared led to a 79% reduction in the risk of progression or death in patients with second-line plus follicular lymphoma. The median progression-free survival was not reached for the experimental arm and it was 11.7 months for the control arm, with a hazard ratio of 0.21, and this was highly statistically significant. 85-plus % of patients were progression-free at 16 months versus 40% of patients in the control arm. And the concordance between independent assessment and investigator assessment were actually excellent at 94%. The study also showed a progression-free survival benefit across a broad number of subsets that were pre-specified, both in terms of demographics, patient characteristics, and also disease characteristics, for example, bulky disease, double refractory disease, POD24, some of the patients that we worry about the most. The study also met its second dual primary endpoint, which was overall response rate with a 95% overall response rate in the experimental arm and a 79% overall response rate in the control arm. Perhaps even more compellingly, the complete metabolic response rate was 83% in the epcoritamab R-squared arm versus 50% in the R-squared arm alone. And both these comparisons were highly statistically significant.

We also looked at, as I said, at a number of other secondary endpoints, duration of response, duration of complete response, were all very much in favor of epcoritamab R-squared compared to R-squared. And a very important point that we made, which is a very patient-centered outcome measure, was the time to next lymphoma therapy. 92, almost 93% of the patients in the epcoritamab R-squared were free of next lymphoma therapy at 16 months versus less than 70% of the patients in R-squared. So that was a large difference. With further follow-up, we’ll fully analyze these results, but this is a very encouraging early look. And then finally, there was a trend towards improved overall survival also with epcoritamab R-squared compared to R-squared. Again, very early look. We did not make, cannot make any statistical claims, but the 16-month overall survival was almost 96% for patients treated with epcoritamab R-squared versus almost 89% in patients treated with R-squared.

We did not see safety signals. The addition of epcoritamab certainly resulted in additional adverse events, but these were all readily manageable, and very few patients discontinued treatment due to adverse event in either arm. In particular, neutropenia and febrile neutropenia were, neutropenia was more with epcoritamab R-squared, but readily managed with GCSF administration, and febrile neutropenia was rare, 6% only. In terms of CRS, or cytokine release syndrome, we didn’t observe higher rates of cytokine release syndrome. We had two step-up dosing cohorts, a two-step-up dosing, and an optimized three-step-up dosing cohorts in the three-step-up dose cohort, which was roughly 130 patients. We observed a reduction in the overall CRS rate at 26%, and only 5% of patients had a grade 2 CRS. There was no grade 3 or grade 4 CRS. There was only one episode of neurotoxicity and really no other adverse events of special interest that were observed in this study. So that was very reassuring to see. This is a treatment regimen that’s administered on a fully outpatient basis. We didn’t hospitalize very many patients, either at baseline or for the management of CRS. The management of CRS required tocilizumab in just a quarter of patients with CRS and corticosteroids in less than 40% of cases.

So overall, epcoritamab R-squared was a superior treatment compared to R-squared. It led to a reduction in the risk of progression of death of 79%, superior overall response rates, superior complete response rate. This was true across all key patient subsets that we analyzed. The added adverse events did not result in treatment interruptions and they were all manageable. So overall, we feel that epcoritamab R-squared really sets a new benchmark as standard of care for the treatment of relapsed/refractory follicular lymphoma in second line and beyond. And I was very pleased to note that on November 18, 2025, the United States FDA granted full approval to epcoritamab R-squared for patients with relapsed/refractory follicular lymphoma. It also secured traditional approval for epcoritamab monotherapy in third-line plus follicular lymphoma. And for those who are interested, all the details of this presentation are available now in The Lancet.

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