COMPARISON OF THE EFFICACY OF EPCORITAMAB VERSUS CHIMERIC ANTIGEN RECEPTOR THERAPIES, POLATUZUMAB‐BASED REGIMENS, AND TAFASITAMAB‐BASED REGIMENS

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Introduction: Epcoritamab, an off-the-shelf subcutaneous CD3xCD20 T-cell–engaging, bispecific antibody that redirects CD3+ T cells to eliminate malignant CD20+ B cells, has shown deep and durable responses in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patient populations, including those with difficult-to-treat LBCL. In the absence of head-to-head trials, there is a need to assess the comparative efficacy of epcoritamab versus novel therapies recently approved for R/R DLBCL. We compared the efficacy of epcoritamab versus chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab-based (pola-based) regimens, and tafasitamab-based (tafa-based) regimens in R/R diffuse large B-cell lymphoma (DLBCL) and LBCL. Methods: This study compared individual patient data from the EPCORE™ NHL-1 trial (NCT03625037; Jan 2022 cutoff) and multiple US academic and community clinical practices in the COTA electronic health records database (2010–2022), including adult patients with R/R DLBCL and LBCL treated with CAR T, pola-based, and tafa-based regimens with ≥2 prior lines of therapy (LOTs). Inverse probability of treatment weighting was used to create balanced cohorts on key demographic and clinical characteristics. Overall response rate (ORR) and complete response (CR) rate were compared using weighted logistic models; progression-free survival (PFS) and overall survival (OS) were compared using weighted Cox proportional-hazard models. Results: A total of 96 CAR T-naive LBCL patients were included in the epcoritamab cohort versus 55 in the CAR T cohort, and 139 DLBCL patients in the epcoritamab cohort versus 37 receiving pola-based and 20 receiving tafa-based regimen. Cohorts were balanced on several factors including but not limited to prior CAR T exposure (in epcoritamab versus pola-based and tafa-based regimens), number of prior LOTs, and refractoriness to last LOT. For epcoritamab versus CAR T, CR rate was 38.9% versus 36.5%. For epcoritamab versus pola-based and tafa-based regimens, CR rate was 38.9% versus 10.7% and 11.2%, respectively. Adjusted odds ratio (95% CI) for CR for epcoritamab versus CAR T was 1.14 (0.79, 1.64; P=0.472); for epcoritamab versus pola-based regimens was 3.60 (2.04, 6.37; P<0.0001); and for epcoritamab versus tafa-based regimens was 3.48 (2.01, 6.01; P<0.0001). Adjusted hazard ratio (95% CI) for OS for epcoritamab versus CAR T was 1.08 (0.70, 1.69; P=0.724); for epcoritamab versus pola-based regimens was 0.44 (0.32, 0.62; P<0.0001); and for epcoritamab versus tafa-based regimens was 0.53 (0.38, 0.75; P=0.0003). Other clinical outcomes are summarized in the Table. Conclusions: Epcoritamab provides significantly better efficacy versus pola-based and tafa-based regimens, with no significant difference versus CAR T, in patients with R/R DLBCL and LBCL who received ≥2 prior LOTs. These findings are subject to limitations consistent with comparative analyses conducted outside of a randomized clinical trial. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Genmab A/S and AbbVie Keyword: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract A. Rosenthal Other remuneration: Educational Sessions: Curio Science, MJH Health Sciences. M. Jun Employment or leadership position: Genmab J. Munoz Consultant or advisory role Pharmacyclics/AbbVie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier, Novartis, MorphoSys/Incyte, Secura Bio, TG Therapeutics, MEI, Lilly/Loxo Honoraria: Targeted Oncology, OncView, Curio, Kyowa, Physicians’ Education Resource, Seattle Genetics Research funding: Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium Other remuneration: Speaker’s Bureau: Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, BeiGene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche. T. Wang Employment or leadership position: Genmab A. Mutebi Employment or leadership position: Genmab A. Wang Employment or leadership position: AbbVie S. Yang Employment or leadership position: Genmab K. Osei-Bonsu Employment or leadership position: AbbVie B. Elliott Employment or leadership position: Genmab A. Kalsekar Employment or leadership position: Genmab F. Rivas Navarro Employment or leadership position: Genmab A. Ip Consultant or advisory role Secura Bio, AstraZeneca, TG Therapeutics Honoraria: Pfizer Other remuneration: Speakers Bureau: Seagen

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