PRECLINICAL EVALUATION OF EPCORITAMAB COMBINED WITH STANDARD OF CARE AGENTS FOR THE TREATMENT OF B‐CELL LYMPHOMAS (2021)

Introduction: B-cell non-Hodgkin lymphoma (B-NHL) has a high unmet medical need for efficacious, well tolerated, off-the-shelf therapies that can combine with standard of care (SOC) regimens. Epcoritamab (DuoBody®-CD3×CD20) is a subcutaneously (SC) administered bispecific antibody with a manageable safety profile and promising preliminary anti-tumor activity in aggressive and indolent B-NHL. Epcoritamab simultaneously binds to CD3 on T cells and CD20 on tumor cells to induce potent T-cell-mediated killing. SOC treatments for B-NHL include GEMOX (gemcitabine and oxaliplatin), or rituximab in combination with chemotherapy regimens such as CHOP (cyclophosphamide [CPA], doxorubicin [DOX], vincristine [VINC] and prednisone [PRD]), bendamustine, or immunomodulatory agents such as lenalidomide (LEN). These therapies have mechanisms of action distinct from epcoritamab and mostly non-overlapping adverse event profiles. Preclinical studies showed that epcoritamab's anti-tumor activity is retained in the presence of a rituximab analog. Here, we present in vitro data of epcoritamab in combination with components of current SOC therapies for B-NHL. Methods: Healthy donor T cells (effector cells) and/or CD20-expressing B-NHL tumor cell lines were pre-treated with SOC components (LEN, CPA, DOX, VINC or PRD) to evaluate the impact on T cells and target cells. Pre-treated T and B-NHL cells were incubated with the same SOC in the presence of epcoritamab, and T-cell-mediated cytotoxicity and associated T-cell activation were assessed by flow cytometry. Bendamustine or GEMOX was added with epcoritamab during the T-cell activation and cytotoxicity assay to assess potential antagonizing effects. Results: LEN 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 could mediate epcoritamab-induced cytotoxicity. Finally, bendamustine and GEMOX did not antagonize T-cell activation and increased T-cell-mediated cytotoxicity induced by epcoritamab. Conclusion: These preclinical data support further exploration of combination of epcoritamab with these SOC agents in clinical trials. Given the promising single-agent activity of SC epcoritamab, and distinct safety profile, these combinations may lead to further deepening of treatment responses and transform long-term outlook for B-NHL patients. Epcoritamab in combination with these SOC agents is currently being evaluated in a clinical trial (NCT04663347). EA – previously submitted to AACR 2021. The research was funded by: Genmab US, Inc. Keywords: Combination Therapies Conflicts of interests pertinent to the abstract C. W Chiu Employment or leadership position: Genmab US, Inc. Stock ownership: Genmab US, Inc. I. H Hiemstra Employment or leadership position: Genmab Stock ownership: Genmab W. ten Hagen Employment or leadership position: Genmab R. Snijdewint-Nkairi Employment or leadership position: Genmab B. de Jong Employment or leadership position: Genmab P. Garrido Castro Employment or leadership position: Genmab C. Kweekel Employment or leadership position: Genmab R. S Oliveri Employment or leadership position: Genmab Stock ownership: Genmab B. Elliot Employment or leadership position: Genmab Stock ownership: Genmab M. Wielgos-Bonvallet Employment or leadership position: Genmab E. Szafer-Glusman Employment or leadership position: Abbvie D. Schuurhuis Employment or leadership position: Genmab J. Blaedel Employment or leadership position: Genmab Stock ownership: Genmab T. Ahmadi Employment or leadership position: Genmab Stock ownership: Genmab E. Breij Employment or leadership position: Genmab Stock ownership: Genmab A K. Sasser Employment or leadership position: Genmab Stock ownership: Genmab M. Jure-Kunkel Employment or leadership position: Genmab Stock ownership: Genmab