Reference: August 2026 | Issue 8 | Vol 12 | Page 35
The CD3×CD20 bispecific antibody (bsAb), epcoritamab, is approved as monotherapy for R/R diffuse large Bcell lymphoma (DLBCL) after at least two prior lines of systemic treatment (pLOTs). Data presented at EHA 2026 compared epcoritamab monotherapy to investigator’s choice chemoimmunotherapy (CIT) of rituximab + gemcitabine/oxaliplatin (R-GemOx) or bendamustine + rituximab (BR) in patients with relapsed/refractory large B cell lymphoma (R/R LBCL).
Eligible patients had CD20+ R/R LBCL, were ineligible for or relapsed after autologous stem cell transplant (ASCT), and had received at least one prior line of systemic treatment.
Patients were randomised 1:1 to epcoritamab monotherapy or CIT. Epcoritamab was administered in 28-day cycles (two step-up doses then 48 mg full doses QW in C1-3, Q2W in C4-9, Q4W in C10+) until disease progression or unacceptable toxicity. R-GemOx was administered as standard Q2W for four 28-day cycles and BR Q3W for six 21-day cycles.
A total of 483 patients were randomised to epcoritamab (n=241), R-GemOx (n=174) and BR (n=68). Median follow-up was 43.2 months. Median age was 71 years, ranging from 28 to 89, and more than half (53 per cent) of patients were from North America/Western Europe. Almost three-quarters (73 per cent) had received at least two pLOTs, and 34 per cent had received three or more pLOTs. More than two-thirds (69 per cent) were refractory to last line of treatment. Fifteen per cent had had prior stem cell transplant (SCT), and 11 per cent had received prior CAR T cell therapy.
A statistically significant improvement in PFS was demonstrated with epcoritamab compared to CIT (HR 0.74; 95% CI 0.60-0.92; P=0.0059). Two-year progression-free survival was 30 per cent versus 13 per cent. Epcoritamab was also associated with higher complete response rates (CRRs) than CIT (38 per cent versus 26 per cent). Durability of response (DOR) was longer with epcoritamab, with a median DOR of 37 months versus six months. Time to next treatment was also longer with epcoritamab versus CIT – seven months versus four months.
Overall response rates were comparable (51 per cent vs 48 per cent) and OS was not significantly different (HR 0.96; 95% CI 0.77-1.20), with 24-month OS of 38 per cent and 33 per cent for epcoritamab and CIT, respectively.
Subsequent treatment with bsAb, CAR T, or SCT was received by 26 per cent in the CIT arm versus 6 per cent in the epcoritamab arm. After post-hoc adjustments for these subsequent treatments and Covid-19-related deaths, the HR for OS favoured epcoritamab (adjusted HR 0.76; 95% CI 0.59-0.99). In patients with one pLOT, trends favoured epcoritamab in terms of PFS (HR 0.67; 95% CI 0.44-1.04), OS (HR 0.80; 95% CI 0.51-1.25), and CRR (45 per cent vs 38 per cent).
Mean treatment duration was longer for epcoritamab compared to CIT (11 months versus two months) and 31 per cent of patients received at least 12 cycles of epcoritamab.
Higher rates of grade 3-4 infections (30 per cent vs 12 per cent) and any-grade Covid-19 (36 per cent vs 11 per cent) were reported in the epcoritamab arm. Grade 5 treatment-emergent adverse events (TEAEs) occurred in 17 per cent of participants in the epcoritamab arm versus 6 per cent in the CIT arm, but these effects largely attributable to grade 5 Covid-19 (9 per cent vs 2 per cent). Cytokine release syndrome was reported in 53 per cent in the epcoritamab arm and immune effector cell associated-neurotoxicity syndrome (ICANS) occurred in 4 per cent.
EPCORE DLBCL-1 is the largest randomised phase 3 trial in R/R LBCL and the first to demonstrate a statistically significant PFS improvement with a CD3×CD20 bsAb monotherapy versus combination CIT.
Compared with CIT, epcoritamab resulted in clinically meaningful improvements in CRR, DOR, and duration of complete response, with less frequent use of subsequent treatment lines. OS was not significantly different – however, the study was conducted during the Covid-19 pandemic and the data is confounded by Covid-19 mortality. Observed AEs were consistent with the established safety profile of epcoritamab.
Reference
Fox CP, et al. Results from EPCORE DLBCL-1: Randomised phase 3 study of epcoritamab (EPCOR) vs investigator’s choice chemoimmunotherapy (CIT) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Abstract S235. European Hematology Association Congress 2026. June 11-14, 2026. Stockholm, Sweden.
