EPCORITAMAB MONOTHERAPY AND COMBINATIONS IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA OR RICHTER’S SYNDROME: NEW ESCALATION AND EXPANSION COHORTS IN EPCORE CLL‐1

Introduction: Targeted therapies have dramatically changed the treatment landscape of chronic lymphocytic leukemia (CLL). Current paradigms include combinations with small molecules (Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors), chemotherapy, anti-CD20 monoclonal antibodies. Although chemotherapy-free regimens, such as single-agent venetoclax + rituximab, shown efficacy in heavily pretreated CLL, disease is generally considered incurable, novel options are needed, especially for patients early relapse, who a poor prognosis very limited later lines therapy. In vitro data support potential bispecific T-cell engagers, but additional clinical needed. Epcoritamab, subcutaneous (SC), T-cell–engaging, antibody, binds to CD3 on T cells CD20 B induce T-cell–mediated killing malignant cells. EPCORE™ CLL-1 trial, epcoritamab monotherapy has manageable safety profile antitumor activity high-risk relapsed or refractory (R/R) CLL (Kater AP et al., ASH 2021) Richter’s syndrome (RS; Kater 2022). Preclinical suggest that may be potentiated by (Mhibik M other standard (Chiu CW AACR 2021), including lenalidomide combination cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), RS, respectively. Here we describe new dose-escalation cohorts expansion arms EPCORE CLL-1. The research was funded by: This study Genmab A/S AbbVie. Keywords: Chronic Lymphocytic Leukemia (CLL), Immunotherapy, Ongoing Trials Conflicts interests pertinent abstract. B. Eichhorst Consultant advisory role AbbVie, AstraZeneca, BeiGene, Janssen, Lilly, MSD Research funding: Roche Educational grants: BeiGene Other remuneration: Roche, MSD: Speakers Bureau H. Eradat Genentech, Incyte, MorphoSys Honoraria: Pharmacyclics MorphoSys, Pharmacyclics, Atara, BMS, Celgene, Gilead, Juno, Kite MorphoSys: C. U. Niemann CSL Behring, Genmab, Takeda, Octapharma Novo Nordisk Foundation T. Oki Employment leadership position: AbbVie A. Kuznetsova M. Rios R. Valentin P. Roche/Genentech, Lava Roche/Genentech Lava: Steering Committee