Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Gemcitabine + oxaliplatin (GemOx) with rituximab, a standard salvage therapy, yields complete response (CR) rates of approximately 30% and median overall survival (OS) of 10-13 months. Patients with refractory disease fare worse, with a CR rate of 7% for subsequent therapies and median OS of 6 months. Epcoritamab, a CD3xCD20 bispecific antibody approved for the treatment of R/R DLBCL after ≥2 therapy lines, has shown promising safety and efficacy in various combinations. We report results from the phase 1b/2 EPCORE® NHL-2 trial evaluating epcoritamab + GemOx in patients with R/R DLBCL who were ineligible for or had failed autologous stem cell transplant (ASCT). Patients received 48-mg subcutaneous epcoritamab after 2 step-up doses until progression or unacceptable toxicity; GemOx was given Q2W for 8 doses. The primary endpoint was overall response rate (ORR). As of December 15, 2023, 103 patients were enrolled (median follow‑up, 13.2 months). Patients had a median age of 72 years and challenging-to-treat disease: ≥2 prior therapy lines, 62%; prior CAR T, 28%; primary refractory disease, 52%; refractory to last therapy, 70%. ORR/CR rates were 85%/61%. Median duration of CR and OS were 23.6 and 21.6 months. Common treatment‑emergent adverse events were cytopenias and cytokine release syndrome (CRS). CRS events had predictable timing, were primarily low grade (52% overall, 1% grade 3), and resolved without leading to discontinuation. Epcoritamab + GemOx yielded deep, durable responses and favorable long-term outcomes in ASCT‑ineligible R/R DLBCL. NCT04663347