Epcoritamab Monotherapy Demonstrates Deep and Durable Responses in Patients With Relapsed or Refractory (R/R) Follicular Lymphoma (FL): 3-Year Follow-Up From EPCORE NHL-1 and EPCORE NHL-3
Introduction/Background/Significance: Epcoritamab is a subcutaneous CD3xCD20 bispecific antibody approved for R/R FL after ≥2 prior lines of therapy (pLOT; 3L+) based on the phase 1/2 trials EPCORE® NHL-1 (NCT03625037; global) and EPCORE NHL-3 (NCT04542824; Japan). We report long-term outcomes with epcoritamab monotherapy (3-year follow-up) from the FL expansion cohorts of these trials (EXP; pooled data) and updated data from the NHL-1 FL cycle 1 optimization cohort (OPT), which evaluated a 3-step-up-dose (3-SUD) regimen to support outpatient epcoritamab administration.
Materials and Methods/Case Presentation/Objective: Adults with CD20+ R/R FL grade (G) 1–3A and ≥2 pLOT received subcutaneous epcoritamab (step-up doses, then 48-mg full doses) until disease progression (PD). Primary endpoints were overall response rate (ORR; EXP) and incidence and severity of CRS (OPT); secondary endpoints included minimal residual disease (MRD) negativity (10−6 cutoff by clonoSeq®; EXP), ORR/CR rate (OPT), and safety (EXP/OPT). Because EXP was conducted during the COVID-19 pandemic, sensitivity analyses with conservative adjustment for COVID-19 deaths were conducted.
Results/Description/Main Outcome Measures: As of December 2024, median follow-up was 35/15.5 months and median treatment duration was 9.7/11.4 months in EXP/OPT. Across EXP (N=149) and OPT (N=86), patients had high-risk disease features (51.5% had POD24 after any first-line treatment; 66.4% had disease refractory to both anti-CD20 and an alkylating agent) and a median of 3 pLOT. In EXP, ORR was 84.6%, CR rate was 67.1%, and MRD-negativity rate was 70.2%. Median duration of CR, progression-free survival, and overall survival were not reached among patients with CR with or without COVID-19 adjustment. Of 100 patients with CR, 35 discontinued treatment for reasons other than PD, had CR at last assessment before discontinuation, and had a response assessment after discontinuation. For these patients, median treatment duration was 18.4 months and 33/35 maintained CR post-discontinuation; median time from discontinuation to last confirmed CR was 13.1 months. Safety in EXP was generally consistent with prior reports. A total of 34.9% of patients had G3–4 infections (18.1% COVID-19), and 7.4% had G5 events (5.4% COVID-19); infections G≥3 occurred in 14.3% of patients on treatment for ≥2 years (n=35). Treatment-emergent AEs (TEAEs) led to epcoritamab discontinuation in 28% (12.1% COVID-19). In OPT, ORR/CR rate was 91.9%/73.3%. Time-to-event data were still maturing at data cutoff; however, an estimated 93% of patients remained alive. CRS and ICANS data remained unchanged with additional follow-up; all CRS was low grade (G1, 39.5%; G2, 9.3%), and no ICANS occurred. Eighteen patients (20.9%) had G3–4 infections (7.0% COVID-19, all G3) and 1 patient had a G5 TEAE (viral respiratory tract infection). TEAEs led to discontinuation in 11.6% of patients (1.2% COVID-19).
Conclusions: With 3 years of follow-up, single-agent epcoritamab demonstrated deep, durable responses in a large, global 3L+ FL population. Safety remained manageable. Response rates were consistent across EXP and OPT, and OPT results confirmed the favorable safety profile of epcoritamab with the 3-SUD regimen, with reduced rates and severity of CRS/ICANS.
Encore statement: Results were previously presented in part at the European Hematology Association Congress; June 12–15, 2025; Milan, Italy.
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