Fixed-Duration Epcoritamab Plus Chemotherapy Yields Response, Remissions in DLBCL

At the American Society of Hematology (ASH) 2025 meeting, updated results from the phase 2 EPCORE NHL‑2 (NCT04663347) trial highlighted the potential of epcoritamab combined with chemotherapy to improve outcomes for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), spanning both high-risk and frail or older populations.

The EPCORE NHL‑2 trial phase 1b/2 enrolled adults with newly diagnosed CD20-positive DLBCL who were ineligible for full-dose R‑CHOP due to age (75 years and older) or age 65 years and older with significant comorbidities.¹ Patients received a fixed-duration regimen of subcutaneous epcoritamab 48 mg combined with R‑mini‑CHOP. Epcoritamab was administered weekly in cycles 1–2, every 3 weeks in cycles 3–6, and every 4 weeks in cycles 7–8, with step-up dosing during the cycle. The primary end point was overall response rate (ORR). Secondary end points included minimal residual disease (MRD) negativity, assessed using the AVENIO Oncology circulating tumor DNA (ctDNA) assay, with MRD negativity defined as less than 1 mutant molecule/mL. Safety, treatment completion, and relative dose intensity of R‑mini‑CHOP were also evaluated.

As of April 9, 2025, 28 patients received epcoritamab plus R-mini-CHOP. Median (IQR) age was 81 (74, 90) years. Most patients (79%) completed treatment, with a median R-mini-CHOP dose intensity of 94% or greater. ORR was 89% and the CR rate was 86%, while the median duration of response and complete response (CR) were not reached. Estimated 2-year progression-free survival (PFS) and overall survival (OS) were 76% and 82%, respectively. MRD negativity was achieved in 95% of evaluable patients, including 93% with International Prognostic Index (IPI) 3 through 5 and 89% with bulky disease; 86% of patients MRD-negative at C3D1 sustained negativity through C6D1. Grade 3 or greater infections occurred in 29% of patients, and 11% discontinued epcoritamab due to treatment-emergent adverse events.

In the second analysis, patients received fixed-duration epcoritamab in combination with 6 cycles of standard R‑CHOP, followed by epcoritamab monotherapy for up to 1 year.² Epcoritamab was administered subcutaneously with step-up dosing during cycle 1 and weekly in cycles 1–4, then every 3 weeks in cycles 5–6, with subsequent monthly monotherapy. The study evaluated efficacy using investigator-assessed ORR as the primary end point. Secondary end points included CR rate, duration of response, PFS and OS, safety, and tolerability. MRD negativity was also assessed.

A total of 47 patients received epcoritamab plus R‑CHOP. Median age was 64 (19, 82) years. IPI scores were 3 in 57% of patients and 4–5 in 38%. After a median follow-up of 38.8 (0.8, 44.3) months, ORR was 98% and CR rate was 85%, with 67% of responses and 75% of CRs ongoing at 33 months.

High CR rates were observed across subgroups (IPI 3, 86% vs IPI 4-5, 83%), age, tumor size, and cell of origin. By cycle 3 day 1, 86% of MRD-evaluable patients were MRD negative, with sustained reductions in ctDNA through cycle 6 day 1. Most patients (94%) completed 6 cycles of R‑CHOP, and 68% completed treatment as planned; among these, 30 of 32 patients had a CR, with 87% maintaining response at a median 25.3-month follow-up. Safety was consistent with prior reports, with serious or grade 3 or greater infections primarily in the first 6 months and no new grade 5 events reported.

References

1. Cheah C, Belada D, Darrah J, et al. Epcoritamab plus R-mini-CHOP results in 2-year remissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida. Poster 64

2. Falchi L, de Vos S, Brody J, et al. Fixed-duration epcoritamab plus R-CHOP in patients with newly diagnosed DLBCL and high IPI scores (3–5) led to sustained remissions and disease-free survival beyond 3 years: Results from the EPCORE NHL-2 trial. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida. Poster 1955