Genmab: Epcoritamab shows high response rates in elderly first‑line DLBCL with mono and R‑mini‑CHOP regimens

Trial populations and design

Two investigator‑led cohorts evaluated subcutaneous epcoritamab in elderly, newly diagnosed CD20+ DLBCL patients ineligible for standard anthracycline regimens. EPCORE DLBCL‑3 (Phase 2) enrolled 66 patients (median age 82.5; 94% with ≥3 comorbidities) for fixed‑duration monotherapy. EPCORE NHL‑2 Arm 8 (Phase 1b/2) enrolled 28 patients for fixed‑duration epcoritamab combined with R‑mini‑CHOP; follow‑up exceeded two years.

Efficacy outcomes

In DLBCL‑3 evaluable patients, overall response rate (ORR) was 67% and complete response (CR) rate 58%; median time to response 1.5 months and to CR 2.2 months. Median duration of response (DOR) and duration of CR (DOCR) were not reached; at 12 months ~67% of responses and 73% of CRs remained ongoing. Median progression‑free survival (PFS) was 13.0 months and median overall survival (OS) was not reached. In NHL‑2 Arm 8, ORR was 93% and CR 86%; median DOR, DOCR, PFS and OS were not reached and two‑year estimated DOR/DOCR were 79%, PFS 76% and OS 82%.

MRD and safety

High rates of minimal residual disease (MRD) negativity were reported: 92% of evaluable responders in DLBCL‑3 and 95% in NHL‑2 Arm 8, typically by Cycle 3 Day 1 and sustained through Cycle 12 Day 1 in most patients. Safety profiles were consistent with prior reports: CRS occurred in 71% (mostly in Cycle 1) and ICANS in 18% in DLBCL‑3; infections (any grade) were 68% with 26% Grade ≥3. In the combination arm the most common Grade ≥3 TEAEs were neutropenia (54%), serious infections (33%) and anemia (14%); TEAEs led to epcoritamab discontinuation in three patients (11%).

Context

Results were presented at the 2026 European Hematology Association (EHA) Congress and the full EPCORE DLBCL‑3 dataset has been published in The Lancet Haematology.