Background
Phase I/II, open-label, dose-escalation and expansion study. 157 patients (expansion cohort) with R/R large B-cell lymphoma (LBCL) after ≥2 prior lines including anti-CD20 and anthracycline; 39% prior CAR-T. Epcoritamab is a bispecific antibody (CD3 × CD20) administered subcutaneously, engaging T cells to kill CD20+ lymphoma cells without manufacturing delay.
Interventions and follow up
Regimen: Epcoritamab 48 mg SC weekly (cycles 1–3), every 2 weeks (cycles 4–9), every 4 weeks thereafter, with step-up dosing in cycle 1 in R/R LBCL after ≥2 prior lines
CRS mitigation: Cycle 1 step-up priming and corticosteroid prophylaxis
Primary endpoint: Overall response rate (independent review committee, LBCL expansion cohort)
Median follow-up: 10.7 months
CRS mitigation: Cycle 1 step-up priming and corticosteroid prophylaxis
Primary endpoint: Overall response rate (independent review committee, LBCL expansion cohort)
Median follow-up: 10.7 months
Results
ORR (primary): 63.1% (95% CI 54.9–70.8%)
CR rate: 38.9%
mDOR (responders): 12.0 months
mDOR (CR patients): Not reached
mPFS: 4.4 months
mOS: 19.0 months
CR rate: 38.9%
mDOR (responders): 12.0 months
mDOR (CR patients): Not reached
mPFS: 4.4 months
mOS: 19.0 months
Adverse events
CRS/ICANS: CRS any grade 49.7%, grade ≥3 2.5%; ICANS any grade 6.4%, grade ≥3 2.5%; no treatment-related deaths from CRS
Hematologic/infectious: Grade ≥3 neutropenia 27.4%; grade ≥3 infection 15.3%
Local: Injection-site reactions 22.3%
Hematologic/infectious: Grade ≥3 neutropenia 27.4%; grade ≥3 infection 15.3%
Local: Injection-site reactions 22.3%
Conclusions
Epcoritamab achieved a 63.1% ORR and 38.9% CR rate in heavily pretreated R/R LBCL, including prior CAR-T failures, with manageable subcutaneous administration. This established epcoritamab as the first CD3×CD20 bispecific antibody approved for this indication.
Key Limitations
Single-arm expansion cohort without a randomized comparator. Short median PFS (4.4 months) reflects a heavily pretreated, partly CAR-T-exposed population, and durability is concentrated in CR patients. Continuous treatment-until-progression schedule contrasts with fixed-duration bispecifics and carries cumulative toxicity/cost. CRS risk requires step-up dosing and monitoring infrastructure. No head-to-head data versus CAR-T or other bispecifics.
Clinical Context
FDA granted accelerated approval of epcoritamab (Epkinly) in May 2023 for R/R DLBCL after ≥2 prior lines; EMA approved (Tepkinly) in 2023. Together with glofitamab, epcoritamab established CD20×CD3 bispecifics as off-the-shelf options for 3L+ R/R LBCL. ESMO and ASCO guidance recognize bispecific antibodies as later-line options, including after CAR-T failure.