Background: Outcomes are poor for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Effective treatments (tx) that drive deep, durable responses and long-term benefit are needed. In the pivotal EPCORE NHL-1 trial (NCT03625037), single-agent epcoritamab (epcor) showed high complete response (CR) and MRD-negativity rates, a median duration of response (mDoR) not reached (NR) in pts who achieved CR, and a manageable safety profile as an off-the-shelf, subcutaneous (SC), CD3xCD20 T-cell–engaging bispecific antibody (Thieblemont et al, JCO 2022). We present updated results with longer follow-up in a challenging-to-treat population. Methods: Pts with R/R CD20⁺ LBCL received SC epcor (step-up priming and intermediate doses followed by 48-mg full doses) in 28-d cycles (Cs): QW, C1–3; Q2W, C4–9; Q4W, C≥10 until PD or unacceptable toxicity. Results: As of Nov 18, 2022, of 157 pts (median age, 64 y) with LBCL (including DLBCL [n=139], HGBCL [n=9], PMBCL [n=4], and FL grade 3B [n=5]; 13/99 double/triple-hit by FISH), 36 remain on tx. Pts had a median of 1.6 y from initial diagnosis to first dose and a median of 3 (range, 2–11) prior tx lines; 61% of pts had primary refractory disease, and 39% had prior CAR T, of whom 75% progressed ≤6 mo of tx. Median follow-up was 20 mo (range, 0.3+ to 28.2). Pts received a mean of 9.1 cycles. LBCL overall response and CR rates were 63.1% and 39.5%, respectively, and were consistent for DLBCL (61.9% and 39.6%). The mDoCR was 20.8 mo. Median time to CR was 2.7 mo; 8 pts converted from partial response to CR at ≥36 wk. Median overall survival (mOS) was 18.5 mo (95% CI, 11.7–NR), with an estimated 58% of pts alive at 12 mo. mOS was NR in pts who achieved CR. Additional outcomes for pts with CR are shown in Table. The most common TEAEs of any grade (G) were: CRS 51%, neutropenia 24%, pyrexia 24%, fatigue 23%, nausea 22%, and diarrhea 21%. Nine pts (6%) had G1–2 ICANS, and 1 pt had a G5 event with confounding factors. Fatal TEAEs occurred in 15 pts; 2 were considered related (COVID-19, ICANS). CRS was predominantly low grade (48% G1–2; 3% G3) and occurred following the first full dose (C1D15). One pt discontinued tx due to G1 CRS. Total metabolic tumor volume (TMTV) data will be presented. Conclusions: These data with longer follow-up reaffirm single-agent SC epcor induces durable CRs with improved outcomes and a manageable safety profile. No new safety signals were observed in these hard-to-treat pts. These impressive data support the ongoing phase 3 studies evaluating epcor across different lines of tx and in various combinations. Clinical trial information: NCT03625037.

Kaplan–Meier estimates.