ASH 2025 | EPCORE FL-1 phase III primary results: Epcoritamab with rituximab + lenalidomide (R2) vs R2 alone for R/R FL

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, the Lymphoma Hub was pleased to speak with Lorenzo Falchi, Memorial Sloan Kettering Cancer Center, New York, US. We asked, What do the primary results from the phase III EPCORE FL-1 trial (NCT05409066) tell us about epcoritamab combined with rituximab + lenalidomide (R2) vs R2 alone in patients with relapsed/refractory follicular lymphoma (R/R FL)?

In this interview, Falchi highlights that epcoritamab and R2 do not have overlapping toxicities and that the combination may offer synergistic activity. He concludes that epcoritamab sets a new benchmark as a readily available treatment for patients with R/R FL.

Key points¹

• The dual primary endpoints for the EPCORE FL-1 trial were overall response rate (ORR) and progression-free survival (PFS) assessed by independent review committee per Lugano criteria.
• Secondary endpoints included complete response rate (CRR), overall survival (OS), duration of response/duration of CR (DoR/DoCR), and safety.
• A total of 488 patients were randomized to receive epcoritamab + R2 (n = 243) or R2 alone (n = 245).
• The ORR and CRR were significantly improved in patients treated with epcoritamab + R2 vs R2 alone (95% vs 79% and 83% vs 50%, respectively; both p < 0.0001).
• Epcoritamab resulted in deep and durable CR, with a median DoR of not reached vs 11.5 months with R2 alone.
• PFS was significantly longer in patients treated with epcoritamab + R2 vs those treated with R2 alone (estimated 16-month PFS rates were 85.5% vs 40.2%), with a 79% risk reduction.
• Higher rates of Grade 3/4 neutropenia and infections were observed with epcoritamab + R2 vs R2 alone (74% vs 52% and 77% vs 53%, respectively); overall adverse events were manageable. Cytokine release syndrome (CRS) was low grade, and the timing was predictable. Few patients discontinued treatment.
• Epcoritamab is the first CD20 x CD3 bispecific antibody to demonstrate clinical benefit over standard of care in a randomized phase III trial in patients with FL.
• Epcoritamab + R2 sets a new benchmark as a readily available, fixed-duration treatment that is suitable for outpatient administration and has the potential to become a new standard of care for patients with R/R FL.

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