EPCORE NHL-6 phase II interim analysis: Outpatient epcoritamab for 2L+ DLBCL

Interim results from EPCORE NHL-6 (NCT05451810), a phase II, open-label, multicenter trial evaluating the outpatient administration and monitoring of subcutaneous epcoritamab after the first full dose (FFD) in 92 adults with second-line or later (2L+) relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL; 2L, n = 42; third-line or later [3L+], n = 50), were published in Clinical Lymphoma, Myeloma & Leukemia by Andorsky et al. Epcoritamab was administered in 28-day cycles with Cycle 1 step-up dosing: a 0.16 mg priming dose on Day 1, a 0.8 mg intermediate dose on Day 8, 48 mg FFD on Day 15, and 48 mg on Day 22. The primary endpoints were Grade ≥3 cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and neurologic events.

Key data: Grade 3–4 treatment-emergent adverse events (TEAEs) occurred in 72.8% of patients, most commonly infections (22.8%), anemia (16.3%), and hyperglycemia (12.0%). Grade 3 CRS and ICANS occurred in 2.2% and 1.1% of patients, respectively. Grade 3 neurologic events were reported in 7.6% of patients, and one patient had a Grade 5 event (cerebrovascular accident). Among 88 patients who received the FFD, 92.0% initiated 24-hour monitoring in the outpatient setting; 29.6% of these patients developed CRS during the FFD period (Day 15–22). Among those who started outpatient monitoring after the FFD, the CRS hospitalization rate was 13.6%. All cases of CRS and ICANS resolved, and none led to treatment discontinuation. The most common neurologic event was headache (20.7%). Investigator-assessed overall response rate (ORR) was 62.0% (95% confidence interval [CI], 51.2–71.9), with complete response (CR) in 42.4% (95% CI, 32.1–53.1). 

Key learning: Outpatient administration and monitoring of epcoritamab after the FFD is feasible in 2L+ DLBCL, with safety and efficacy consistent with the pivotal EPCORE NHL-1 trial, supporting broader access across academic and community settings.