Updated Results from EPCORE NHL-6: Phase 2 Study of Subcutaneous Epcoritamab as Outpatient Treatment for 2L+ Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)
Introduction/Background/Significance: Currently approved bispecific antibodies for R/R DLBCL require inpatient monitoring. Epcoritamab is a CD3×CD20 bispecific antibody approved for R/R DLBCL administered subcutaneously with recommended inpatient monitoring for 24 hours after the first full dose. The NHL-6 trial (NCT05451810) investigated the feasibility to dose and monitor 2L+ DLBCL patients in the outpatient setting for the first full dose.
Materials and Methods/Case Presentation/Objective: Patients at US sites received epcoritamab in 28-day cycles (C): two C1 step-up doses (0.16 mg, 0.8 mg) then full dose at C1D15 and thereafter (48 mg); C1-3, QW; C4-9, Q2W; C≥10, Q4W. Primary endpoints were grade 3+ cytokine release syndrome (CRS), immune cell-associated neurotoxicity syndrome (ICANS), and neurologic events. Patients received safety education materials and mandatory CRS prophylaxis during C1. Responses were investigator-assessed per Lugano criteria.
Results/Description/Main Outcome Measures: At the 15 January 2025 cutoff, 92 patients received ≥1 epcoritamab dose (community sites, n=41; academic sites, n=51); 42 were 2L patients (45.7%). Median age was 69.0 years; 82.6% had Ann Arbor Stage III-IV, 23.9% had prior CAR-T, 23.9% had bulky disease ≥7 cm, and 51.1% had International Prognostic Index ≥3. Median follow-up was 7.6 months (95% CI: 6.0-9.2) and 50.0% remained on treatment. CRS occurred in 40.2% (Grade 1, 21.7%; Grade 2, 16.3%; Grade 3, 2.2%); all resolved, none led to discontinuation, and median time to resolution was 2 days. ICANS occurred in 7.6% (Grade 1, 4.3%; Grade 2, 2.2%; Grade 3, 1.1%); median time to resolution was 3 days; all events resolved, and none led to treatment discontinuation. Among 88 patients who received the first full dose, 81 were monitored as outpatient and 7 as inpatient (2 were already admitted, 5 were admitted at investigator discretion). After the first full dose, CRS occurred in 31.8% (Grade 1, 17.0%; Grade 2, 13.6%; Grade 3, 1.1%; median time to onset 24.8 hours) and ICANS in 3.4% (Grade 1, 1.1%; Grade 2, 2.3%; median time to onset 126.1 hours). Overall response rate was 62.0% with 42.4% complete response rate. Additional data by subgroups will be presented.
Conclusions: The incidence and severity of CRS and ICANS were consistent with previous data from EPCORE NHL-1. Our results support the feasibility of outpatient administration and monitoring of epcoritamab in 2L+ DLBCL with no mandatory hospitalization required after the first full dose in this study. This abstract was accepted for presentation at the 2025 annual meeting of the Society of Hematologic Oncology.
