Interim results from the ongoing phase 2 EPCORE DLBCL-3 study (NCT05660967) found fixed-duration subcutaneous epcoritamab monotherapy demonstrates durable responses with manageable safety among elderly patients with previously untreated diffuse large B-cell lymphoma (DLBCL) who are ineligible for anthracycline-based chemotherapy.

These results will be presented by Umberto Vitolo, MD, Candiolo Cancer Institute, Candiolo, Italy, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.

Researchers conducted a phase 2 trial to determine the safety and efficacy of epcoritamab monotherapy for patients with DLBCL as a first-line treatment. Patients received a step-up epcoritamab dosing regimen followed by 48 mg subcutaneously weekly during cycles 1 to 3 and every 4 weeks in cycles 4 to 12. The primary end point was complete response (CR) rate, and the secondary end point was minimal residual disease (MRD) negativity.

Overall, a total of 66 patients received epcoritamab across stage 1 (n = 44) and stage 2 (n = 22). The median age of all patients was 82.5 years (range, 76 to 95). All patients had at least 1 comorbidity, including frequent cardiac (41%), vascular (80%), renal (64%), and neurological disorders (32%). About 62% of patients had stage IV disease, 64% had IPI scores ≥3, and 33% had bulky disease (≥7 cm).

The median follow-up was 14.9 months (95% confidence interval [CI], 11.8 to 16.7). At data cutoff, 30% of patients had completed treatment, 21% remained on therapy, and 48% had discontinued treatment. Treatment discontinuation was most commonly due to disease progression (23%) or adverse events (14%).

The overall response rate (ORR) was 70%, and the CR rate was 58%. The median time to response was 1.5 months (range, 1.2 to 3.4), and the median time to CR was 2.2 months (range, 1.2 to 5.4). The median progression-free survival (PFS) rate was 13.0 months (95% CI, 5.4 to not reached), and the median OS was not reached.

Minimal residual disease (MRD) negativity at any point was achieved in 88% of MRD-evaluable responders. MRD negativity was detected as early as cycle 3 day 1 and was sustained through cycle 12 in the majority of patients with longitudinal samples. Additionally, MRD-negative patients demonstrated longer PFS rates.

In terms of safety, treatment-emergent adverse events occurred in 94% of patients. The most common treatment-emergent adverse events were cytokine release syndrome (CRS; 70%), diarrhea (23%), and fatigue (21%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 18% of patients and were primarily grade 1 or 2. Grade ≥ 3 infections occurred in 18% of patients.

These results support epcoritamab as an effective, chemotherapy-free option for elderly and comorbidity-burdened patients with 1L LBCL. The high response rates, early and sustained MRD negativity, and outpatient administration highlight its potential as a new frontline approach for patients unable to tolerate standard chemoimmunotherapy.

The researchers concluded, “Fixed-duration [epcoritamab] monotherapy demonstrated robust efficacy (ORR, 70%), with early, deep, and durable responses in elderly [patients] with 1L LBCL and comorbidities, a population with significant unmet need and poor outcomes.”

They added, “These findings, together with those from other trials (EPCORE NHL-2; NCT04663347) show that [epcoritamab], as monotherapy or combined with other [treatment], can be a favorable option for [patients] with 1L DLBCL across a broad range of ages and fitness levels.”

Source:

Vitolo U, Duell J, Burgues JM, et al. Fixed-duration epcoritamab monotherapy induces high response and MRD-negativity rates in elderly patients with newly diagnosed large B-cell lymphoma (LBCL) and comorbidities: Results from EPCORE DLBCL-3. Dec 6-9, 2025; Orlando, FL. Abstract: 63