Efficacy and safety of epcoritamab in relapsed or refractory large B-cell lymphoma: 3-year update from the EPCORE NHL-1 trial.

Epcoritamab, a CD3xCD20 bispecific antibody, resulted in deep, durable responses with a manageable safety profile in patients with relapsed/refractory large B-cell lymphoma (LBCL) in EPCORE® NHL-1 (NCT03625037). We report results from a 3-year follow-up. Adults with relapsed/refractory LBCL received epcoritamab until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Median age was 64.0 years, 39% of patients received prior CAR T-cell treatment, and 75% were refractory to ≥ 2 consecutive lines of treatment. As of May 3, 2024 (median follow-up 37.1 months [range, 0.3–45.5]), ORR was 59% and complete response (CR) rate 41% by investigator assessment. Median duration of response was 20.8 months (95% confidence interval [CI], 13.0–32.0). Median duration of CR was 36.1 months (20.2–not reached [NR]); the longest ongoing CR was > 43 months. Median progression-free survival was 4.2 months (95% CI, 2.8–5.5) in all patients and 37.3 months (26.0–NR) in patients with CR. Median overall survival was 18.5 months (95% CI, 11.7–27.7) in all patients and NR in patients with CR. Of 119 patients evaluable for minimal residual disease (MRD) assessments, 54 (45%) were MRD-negative at any time during the study. Most common adverse events were cytokine release syndrome (51%), fatigue (25%), and pyrexia (25%), with no new safety signals. Grade 1, 2, and 3 infections occurred in 23%, 34%, and 24% of patients, respectively. The durability of responses and prolonged survival in complete responders suggest long-term disease-free survival with epcoritamab in these patients with relapsed/refractory LBCL.