Primary Results From EPCORE FL-1 Presented at ASH 2025

Urshila Durani, MD, MPH Mayo Clinic | Joshua Brody, MD Mount Sinai Icahn School of Medicine

December 17, 2025

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Key Points

  • Epcoritamab plus rituximab and lenalidomide received approval for patients with relapsed or refractory follicular lymphoma based on results from the EPCORE FL-1 study.

  • In the primary analysis, epcoritamab was associated with significantly improved response rates and progression-free survival (PFS).

  • The epcoritamab triplet was associated with higher rates of neutropenia and infection, but was not prohibitively more toxic than rituximab and lenalidomide alone.

Urshila Durani, MD, MPH, of Mayo Clinic, and Joshua Brody, MD, of Mount Sinai, met to discuss the primary phase 3 data from the EPCORE FL-1 trial presented at the 2025 ASH Annual Meeting (ASH 2025). EPCORE FL-1 evaluated rituximab and lenalidomide with or without epcoritamab in patients with relapsed or refractory follicular lymphoma. The FDA previously approved epcoritamab in November 2025 based on early data from the study.

Primary EPCORE FL-1 Data at ASH 2025

The EPCORE FL-1 trial randomized 488 patients to either epcoritamab plus rituximab and lenalidomide (n=243) or rituximab and lenalidomide (n=245). The dual primary end points were PFS and overall response rate (ORR), and secondary end points included complete response (CR) rate, overall survival, duration of response (DOR), and safety.

In a preplanned interim analysis of the first 232 patients that reached 12 months of follow-up, the ORR in the epcoritamab arm was 95.7% (95% CI, 90.2-98.6) versus 81% (95% CI, 72.7-87.7; P < .0001) in the control arm. The 12-month DOR was 91.4% (95% CI, 84.0-95.4) with epcoritamab versus 57% (95% CI, 44.2-68.0) with control. In the full study population, PFS was significantly increased in the epcoritamab arm compared with the rituximab and lenalidomide only arm (hazard ratio, 0.21; 95% CI, 0.13-0.33; P < .0001), according to the ASH 2025  presentation. The epcoritamab arm had a CR rate of 74.5% (95% CI, 68.5-79.8) versus 43.3% (95% CI, 37.0-49.7; P < .0001) in the control arm.

EPCORE FL-1 Toxicity Profile

Overall, 88.1% of patients in the epcoritamab arm versus 62.2% in the rituximab and lenalidomide arm reported grade 3 or 4 treatment-emergent adverse events (TEAEs). The difference was primarily driven by increased rates of neutropenia (66.3% vs 37.8%) and infections (29.2% vs 13.4%) with epcoritamab versus control. In the epcoritamab and control arms, grade 3 or 4 febrile neutropenia occurred in 6.2% versus 2.1% of patients, and TEAEs leading to discontinuation occurred in 16% versus 11.8% of patients, respectively.

Dr. Durani questioned whether the escalated EPCORE FL-1 regimen is appropriate for allpatients with relapsed or refractory follicular lymphoma given the long course of disease. Although the regimen might not be necessary for every patient, much of the toxicity is attributed to rituximab and lenalidomide. Therefore, patients healthy enough for the doublet are likely healthy enough for the triplet, Dr. Brody said.