DP008 | EPCORE DLBCL-3: FIXED-DURATION EPCORITAMAB MONOTHERAPY IN OLDER (≥75 Y), ANTHRACYCLINE-INELIGIBLE PATIENTS WITH PREVIOUSLY UNTREATED LARGE B-CELL LYMPHOMA

Introduction: Patients (pts) with newly diagnosed (1L) LBCL and advanced age or comorbidities, who are ineligible for anthracycline-based treatments (tx) like R[mini]-CHOP, have limited options and poor outcomes. Epcoritamab (epcor), a CD3xCD20 bispecific antibody, is approved for relapsed/refractory LBCL after ≥2 lines of tx. The phase 2 EPCORE DLBCL-3 (NCT05660967) trial evaluates fixed-duration epcor monotherapy or epcor+lenalidomide in anthracycline-ineligible pts with 1L LBCL. We report efficacy and safety from the epcor monotherapy arm. Methods: Pts with 1L CD20⁺ LBCL ineligible for anthracycline-based tx (age ≥80y or ≥75y with comorbidities), received step-up doses of subcutaneous epcor (0.16mg on cycle [C]1 day [D]1 and 0.8mg on C1D8) followed by 48mg for up to 1y (28-d C; QW in C1–3, Q4W C4–12). Primary endpoint was complete response (CR) rate per Lugano criteria. Results: As of 21 Sep 2024, 45 pts were randomized to epcor monotherapy; 44 received tx. Median age was 81y (range, 77–95), 38% were ≥85y, 56% had Ann Arbor stage IV disease, 29% bulky disease (≥7 cm), 73% renal impairment, 87% cardiac and/or cardiovascular disorders, 40% had other comorbidities precluding chemotherapy use. At data cutoff, the median follow-up (FU) was 9.5mo (range, 0.4–17.7); 20% of pts completed tx, 32% remained on tx, and 48% had discontinued (d/c) tx. The Table below presents key efficacy endpoints. Of 15 responders (14 with CR, 1 with partial response) evaluated for minimal residual disease (MRD), 93% (14/15) were MRD-negative at any time. Most common tx-emergent adverse events (TEAEs) were CRS (71%), fatigue (23%), and constipation (23%). CRS was mainly G1 (39%)/G2 (27%); 5% had a G3 event; 97% of events occurred in C1. 8 pts (18%) had a serious infection, including 4 (9%) with serious COVID-19. 7 pts had ICANS (7% G1, 7% G2, 2% G3); all ICANS events resolved after a median of 2d (range, 1–22). 4 pts (9%) had neutropenia, with no cases of febrile neutropenia. 8 pts (18%) d/c tx due to TEAEs; 5 fatal TEAEs occurred (COVID-19 [n=2], CMV reactivation, tumor lysis syndrome, and tumor hemorrhage). Conclusions: Fixed-duration epcor monotherapy led to high response rates and a manageable safety profile in older, anthracycline-ineligible pts with 1L LBCL, indicating that epcor monotherapy is a promising chemotherapy-free tx option for these pts with a significant unmet need and historically poor outcomes. ©International Conference on Malignant Lymphoma 2025. Reused with permission.