ZUMA‐23: A GLOBAL, PHASE 3, RANDOMIZED CONTROLLED STUDY OF AXICABTAGENE CILOLEUCEL VERSUS STANDARD OF CARE AS FIRST‐LINE THERAPY IN PATIENTS WITH HIGH‐RISK LARGE B‐CELL LYMPHOMA

Introduction: The nearly 40% of patients with large B-cell lymphoma (LBCL) who are refractory to or relapse after current first-line standard-of-care (SOC) regimens, such as R-CHOP (rituximab [R] + cyclophosphamide [C], doxorubicin [H], vincristine [O], and prednisone [P]) DA-EPOCH-R (dose-adjusted etoposide [DA-E]), have poor prognoses. High International Prognostic Index (IPI) score the subtype high-grade (HGBL) associated shorter progression-free overall survival (PFS OS; Nastoupil LJ Bartlett NL. J Clin Oncol. 2023). Strategies improve outcomes in these subgroups been largely unsuccessful; therefore, therapeutic options a different mechanism action needed. Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved treat relapsed/refractory LBCL demonstrating significant clinical benefit second line (ZUMA-7; Locke FL, et al. N Engl Med. 2022) third above (ZUMA-1; Neelapu SS, 2017) therapy. Additionally, Phase 2 ZUMA-12 study LBCL, axi-cel showed high rate durable responses objective response 89% (complete rate, 78%) ongoing 73% (median follow-up, 15.9 months; Nat 2022). ZUMA-23 first 3, randomized controlled evaluate CAR regimen for any cancer will assess versus SOC high-risk defined IPI 4–5. Methods: 3 trial design enroll ≈300 adult high-risk, histologically confirmed based on 2016 WHO classification, including diffuse lymphoma, HGBL, transformed follicular marginal zone (Swerdlow SH, Blood. 2016). Eligible receive 1 cycle R-chemotherapy then be 1:1 continue SOC. Patients arm undergo leukapheresis bridging therapy, followed by lymphodepleting chemotherapy (fludarabine/cyclophosphamide), single infusion (2×106 T cells/kg). Prophylactic corticosteroids may administered reduce incidence severity cytokine release syndrome at investigator’s discretion. 5 additional cycles (investigator’s choice). primary endpoint event-free blinded central review. Key secondary endpoints OS PFS. Safety, quality life, pharmacokinetics also assessed. history HIV and/or hepatitis B C undetectable viral loads enroll. exclusion criteria include nervous system. open enrollment (NCT05605899). Encore Abstract—previously submitted ASCO 2023 EHA research was funded by: Kite, Gilead Company. Keywords: aggressive non-Hodgkin cellular therapies, trials Conflicts interests pertinent abstract J. Westin Consultant advisory role Bristol Myers Squibb, Genentech, Company Research funding: ADC Therapeutics, AstraZeneca, Calithera, Kymera, Morphosys/Incyte, Novartis C. A. Jacobson Company, Novartis, BMS/Celgene, Instill Bio, ImmPACT Lonza, Ipsen, Epizyme Blubird Daiichi-Sankyo Honoraria: Epizyme, BlueBird Kite Pfizer Chavez AdiCet, GenMab, Janssen, Merck Other remuneration: Speakers’ bureau participation BeiGene Lilly Sureda Abbvie, Squibb/Celegen, Milteny, MSD, Takeda Squibb/Celgene, Pierre FabreTakeda Educational grants: F. Morschhauser AbbVie, Bristol-Myers Sciences, Roche Speakers' Roche; expert testimony Genentech B. Glaß Employment leadership position: Helios Klinik Berlin-Buch Riemser M. Dickinson Davies Genmab, Incyte, Cellcentric, I. W. Flinn BeiGene, Century Hutchison MediPharma, InnoCare Pharma, Myeloid Secura Servier Pharmaceuticals, TG Vincerx Xencor 2seventy bio, Acerta Agios, ArQule, Biopath, CALIBR, CALGB, Celgene, City Hope National Medical Center, Constellation Curis, CTI Biopharma, Fate Forma Forty Seven, IGM Biosciences, Infinity Loxo, Marker Merck, Millennium MorphoSys, Nurix, Pfizer, Pharmacyclics, Portola Rhizen Roche, Seattle Genetics, Step Tessa Trillium Triphase & Development Corp., Unum Verastem, Pharma D. G. Maloney A2 Biotherapeutics, Amgen, Juno Legend Biotech, Mustang Navan Technologies, Umoja (To your institution): Juno, Data Safety Monitory Board Advisory Bioline Rx Celgene; rights royalties from Fred Hutch patents licensed Juno; stock Biotherapeutics Technologies Chamuleau Abbvie Xue Stock ownership: Biogen, S. Shahani Amgen; other relationship O. Nikolajeva IQVIA, Kang Kaplan Schupp Inc. H. Miao E. Rich