Abstract 1574: Preclinical evaluation of epcoritamab combined with standard of care therapies for the treatment of B-cell lymphomas

Abstract

Abstract B-cell non-Hodgkin lymphoma (B-NHL) is a heterogeneous disease with an unmet medical need for new efficacious, well tolerated, off-the-shelf therapies that can combine with standard of care (SOC) regimens. Epcoritamab (GEN3013; DuoBody®-CD3×CD20) is a novel subcutaneously administered bispecific antibody with a manageable safety profile and promising preliminary anti-tumor activity in both aggressive and indolent B-NHL. Epcoritamab simultaneously binds to CD3 on T cells and to CD20-expressing tumor cells to induce potent T-cell-mediated killing. SOC treatments for B-NHL include rituximab in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), bendamustine, or immunomodulatory agents such as lenalidomide. These therapies have mechanisms of action distinct from that of epcoritamab, and mostly non-overlapping adverse event profiles. Previous preclinical studies demonstrated that epcoritamab can induce effective anti-tumor activity in the presence of a rituximab analog, supporting the combination of the two in clinical trials. Here, we present in vitro studies conducted to evaluate whether epcoritamab can be used in combination with current SOC therapies for B-NHL. Healthy donor T cells as effector cells and/or CD20-expressing B-NHL tumor cell lines were pre-treated with each individual SOC component (lenalidomide, cyclophosphamide, doxorubicin, vincristine, prednisone) to evaluate the impact on T cells and target cell lines. Next, co-cultures of pre-treated T and B-NHL cells were incubated with the same SOC component in the presence of epcoritamab, and T-cell mediated cytotoxicity and associated T-cell activation were assessed by flow cytometry. Bendamustine was added together with epcoritamab during the T-cell activation and cytotoxicity assay to assess potential antagonizing effect. Lenalidomide enhanced T-cell activation induced by CD3 crosslinking with immobilized anti-CD3 or epcoritamab, resulting in higher potency of these T cells to exert epcoritamab-induced cytotoxicity of CD20-expressing tumor cells. T cells pre-treated with individual CHOP components were capable of mediating epcoritamab-induced cytotoxicity. Finally, bendamustine did not antagonize T-cell activation and had an additive effect on T-cell-mediated cytotoxicity by epcoritamab. These preclinical data indicate that epcoritamab-can be combined with these SOC agents. In conclusion, these data warrant clinical evaluation of epcoritamab combinations with multiple SOC therapies. Given the promising single-agent activity of epcoritamab, these combinations may lead to deep and durable responses that can translate into improved long-term outcomes for B-NHL patients. Epcoritamab combination therapies are planned to be evaluated in a clinical trial sponsored by Genmab and Abbvie. Citation Format: Christopher W. Chiu, Ida H. Hiemstra, Wessel ten Hagen, Rajaa Snijdewint-Nkairi, Bart de Jong, Roberto S. Oliveri, Brian Elliot, Edith Szafer-Glusman, Danita Schuurhuis, Julie Blaedel, Tahamatan Ahmadi, Esther Breij, A. Kate Sasser, Maria Jure-Kunkel. Preclinical evaluation of epcoritamab combined with standard of care therapies for the treatment of B-cell lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1574.