PHASE 3 TRIAL OF SUBCUTANEOUS EPCORITAMAB + R‐CHOP VERSUS R‐CHOP IN PATIENTS (PTS) WITH NEWLY DIAGNOSED DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL): EPCORE DLBCL‐2

Introduction: In pts with newly diagnosed DLBCL, standard treatment rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has a 5-year progression-free survival (PFS) rate of 67.0%, 58.4%, 45.8% for International Prognostic Index (IPI) 2, 3, 4–5, respectively (Ruppert et al., Blood 2020). Epcoritamab is subcutaneously administered, bispecific antibody that binds CD3 on T cells CD20 B cells, inducing potent selective T-cell–mediated killing malignant CD20+ (Hutchings Lancet 2021). monotherapy demonstrated deep durable responses (overall response [ORR], 63%; complete rate, 39%; median duration response, 12 months) was generally well tolerated in relapsed/refractory (R/R) aggressive, large B-cell lymphoma (LBCL) (Thieblemont J Clin Oncol 2022). Results from an ongoing phase 1/2 study high-risk DLBCL (EPCORE NHL-2 arm 1; NCT04663347) show epcoritamab + R-CHOP promising efficacy manageable safety profile IPI 3–5. Among efficacy-evaluable (n = 31), ORR 100% metabolic (CMR) 77%; cytokine release syndrome (CRS) events 17/33; 52%) were mostly low-grade, had predictable timing, did not lead to discontinuation (Falchi ASCO 2022, abstract 7523). These encouraging data support further evaluation the DLBCL. Methods: This global, multicenter, open-label (NCT05578976) evaluates adults one following (de novo or transformed follicular [FL]): 1) otherwise specified (NOS); 2) high-grade MYC BCL-2 and/or BCL-6 rearrangement; 3) T-cell/histiocyte–rich LBCL; 4) Epstein-Barr virus–positive NOS; 5) FL grade 3b. Other key eligibility criteria include ≥2 (pts 2 exceed ∼30% total pts), ECOG PS 0–2, ≥1 measurable disease site. Approximately 900 will be randomized 2:1 either (6 cycles, followed by cycles epcoritamab) rituximab). The primary endpoint PFS 3–5 (based IRC assessment per Lugano criteria). secondary endpoints are 2–5, event-free survival, CMR, overall minimal residual negativity. Safety incidence severity treatment-emergent adverse (AEs), serious AEs, AEs special interest (CRS, immune cell–associated neurotoxicity syndrome, clinical tumor lysis syndrome). Enrollment began January 2023 globally. © American Society Clinical Oncology, Inc. Reused permission. accepted previously presented at Annual Meeting. All rights reserved. research funded by: AbbVie Genmab. Keywords: aggressive non-Hodgkin lymphoma, combination therapies, immunotherapy Conflicts interests pertinent abstract. L. H. Sehn Consultant advisory role AbbVie, Amgen, AstraZeneca, BeiGene, BMS/Celgene, Genentech/Roche, Incyte, Janssen, Kite/Gilead, Merck, Seattle Genetics Research funding: Teva, Roche/Genentech M. Chamuleau Novartis, Incyte BMS, Gilead, GenMab G. Lenz Roche, Bayer, Genmab, Karyopharm, Constellation, ADC Therapeutics, Sobi, Miltenyi, PentixaPharm, Genase, Immagene, Hexal, Lilly MorphoSys, AstraZeneca remuneration: Invited Speaker: Hexal R. Clausen Janssen Kite/Gilead C. Haioun Miltenyi A. Davies Honoraria: Kite, Genmab MSD, Cellcentric Educational grants: Roche T. Oki Employment leadership position: E. Szafer-Glusman Conlon Stock ownership: Chiou D. Ipe B. Elliot J. Wu Salles Epizyme, Loxo, Rapt, Regeneron, Takeda