DP074 | EPCORITAMAB MONOTHERAPY DEMONSTRATES DEEP AND DURABLE RESPONSES AT 3-YEAR FOLLOW-UP IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA

Introduction: Epcoritamab (epcor), a subcutaneous CD3xCD20 bispecific antibody, is approved for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy (3L+) based on EPCORE NHL-1 FL (NCT03625037; US/EU) and NHL-3 FL (NCT04542824; Japan) expansion cohorts (EXP) results. We report 3-y follow-up (FU) from EXP and updated NHL-1 cycle (C) 1 optimization cohort (OPT) results for epcor monotherapy in patients (pts) with 3L+ FL. Methods: Pts with 3L+ CD20+ R/R FL grade (G) 1–3A received epcor in 28-d Cs until disease progression (PD) or unacceptable toxicity. NHL-1 (N=128) and NHL-3 (N=21) EXP were pooled for diversity; OPT is reported separately. Primary endpoints were efficacy (EXP) and CRS incidence and severity (OPT); secondary endpoints were MRD (ClonoSeq®) negativity (EXP), response rates (OPT), and safety (EXP/OPT). Results: As of Dec 2024, median FU was 35 mo and 15.5 mo, and median treatment (tx) duration was 9.7 and 11.4 mo, in EXP (N=149) and OPT (N=86), respectively. Pts had a median of 3 prior lines of tx and high-risk disease features. In pooled EXP, ORR/CRR were 84.6%/67.1% (Table). With longer-term FU, safety from EXP was consistent with previous reports. In EXP, conducted during the COVID-19 pandemic peak, 34.9% of pts had G3-4 infections (18.1% COVID-19) and 7.4% had G5 events (5.4% COVID-19); 28% of pts discontinued (d/c) tx due to tx-emergent adverse events (TEAEs; 12.1% COVID-19). Among 35 pts on ≥2y of tx, 14.3% had G3 or higher infections. In OPT, updated ORR/CRR were 91.9%/73.3%; time-to-event endpoint data were still maturing, with 93% of pts alive. Safety from OPT remained unchanged from prior reports of only low-grade CRS (39.5% G1, 9.3% G2) and no ICANS. In OPT, conducted post COVID-19 pandemic peak, 20.9% of pts had G3-4 infections (7.0% COVID-19, all G3); 1 pt had G5 TEAE of viral respiratory tract infection. TEAEs leading to tx d/c occurred in 11% (1.2% COVID-19). Conclusions: Epcor monotherapy demonstrated deep, durable responses and manageable safety with no new safety signals at 3y in a large and diversified 3L+ FL global population. OPT cohort response rates were consistent with those from EXP and confirmed the favorable safety profile of epcor, with reduced rates and severity of CRS/ICANS with 3-SUD regimen, and lower post-pandemic COVID-19 rates. ©2025 European Hematology Association. Reused with permission. This abstract was accepted at the 2025 EHA Annual Meeting.