Phase II EPCORE DLBCL-3 trial: Epcoritamab ± lenalidomide in older patients with DLBCL

Results from the open-label, randomized, phase II EPCORE DLBCL-3 trial (NCT05660967), evaluating fixed-duration epcoritamab ± lenalidomide as first-line therapy in 108 patients with newly diagnosed (ND) diffuse large B-cell lymphoma (DLBCL) ineligible for anthracycline-based chemoimmunotherapy (aged ≥80 years or ≥75 years with clinically significant comorbidities), were published in The Lancet Haematology by Vitolo et al. In Stage 1, patients were randomized to receive epcoritamab monotherapy (n = 44) or epcoritamab + lenalidomide (n = 44); based on the interim analysis of Stage 1, epcoritamab monotherapy was selected for Stage 2 (n = 22). The primary endpoint was investigator-assessed complete response (CR) rate. 

Key data: In Stage 1, the CR rate in the epcoritamab monotherapy group was 63.6% (95% confidence interval [CI], 47.8–77.6) vs 45.5% (95% CI, 30.4–61.2) in the epcoritamab + lenalidomide group. The overall response rates (ORRs) were 70.5% (95% CI, 54.8–83.2) vs 59.1% (95% CI, 43.2–73.7) in the epcoritamab monotherapy vs epcoritamab + lenalidomide groups. In Stage 2 (epcoritamab monotherapy), the CR rate was 45.5% (95% CI, 24.4–67.8). Across Stages 1 and 2, the CR rate, ORR, and median progression-free survival (PFS) in patients receiving epcoritamab monotherapy were 57.6% (95% CI, 44.8–69.7), 66.7% (95% CI, 54.0–77.8), and 13.0 months (95% CI, 5.6–not reached [NR]), respectively. Across Stages 1 and 2, the most common Grade ≥3 treatment-emergent adverse events (TEAEs) in the monotherapy group were infections (24%), neutropenia (12%), and hypertension (11%). Any-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 71% and 18% of patients, respectively.

Key learning: Fixed-duration epcoritamab monotherapy demonstrated promising response rates and a manageable safety profile in older patients with ND DLBCL, supporting its continued investigation as a first-line chemotherapy-free treatment option in this population.