PRIMARY OVERALL SURVIVAL ANALYSIS OF THE PHASE 3 RANDOMIZED ZUMA‐7 STUDY OF AXICABTAGENE CILOLEUCEL VERSUS STANDARD OF CARE IN RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA

Introduction: In ZUMA-7 (NCT03391466), axicabtagene ciloleucel (axi-cel) was superior to a chemotherapy-based standard of care (SOC; hazard ratio [HR]: 0.398; p < 0.0001) in the primary analysis of event-free survival (EFS) as second-line therapy in patients with early relapsed or refractory large B-cell lymphoma (LBCL; Locke et al. NEJM. 2022). In a preplanned interim analysis, median overall survival (OS) was numerically prolonged in the axi-cel arm (Locke et al. TCT 2022. Abstract 1). We now report the primary analysis of OS from ZUMA-7. Methods: Study procedures and eligibility were previously reported. The intention-to-treat (ITT) primary OS analysis occurred 5 years after the first patient was randomized (01/25/2018) per protocol. A log-rank test stratified by randomization stratification factors compared OS between the 2 arms. In addition to the ITT analysis, prespecified OS sensitivity analyses were conducted to adjust for confounding due to subsequent cellular immunotherapy in the SOC arm. Other endpoints included progression-free survival (PFS) per investigator assessment, OS in key subgroups, and safety. Exploratory analyses were conducted to determine the association between OS and axi-cel pharmacokinetics and product features. Results: In total, 359 patients were randomized, 180 to axi-cel and 179 to SOC. As of 01/25/2023, at a median follow-up of 47.2 mo, axi-cel demonstrated a statistically significant improvement in OS over SOC (HR: 0.726, 95% CI: 0.540–0.977; stratified log-rank 1-sided p = 0.0168 [efficacy boundary, 0.0249]). Median OS was prolonged with axi-cel versus SOC (not reached vs. 31.1 mo, respectively); 48-mo OS estimates were higher with axi-cel (54.6% vs. 46.0%, respectively). OS benefit with axi-cel versus SOC was consistent in prespecified key subgroups, including age ≥65 years, primary refractory, early relapse, high-grade B-cell lymphoma, and high second-line age-adjusted IPI. In the SOC arm, 102 (57%) patients received subsequent cellular immunotherapy off protocol. Prespecified OS sensitivity analyses showed an even greater OS benefit with axi-cel versus SOC, with stratified HR of 0.608 (95% CI: 0.449–0.824) by Rank-Preserving Structural Failure Time model. PFS by investigator confirmed benefit of axi-cel over SOC (HR: 0.506, 95% CI: 0.383–0.669), with 48-mo PFS estimates of 41.8% versus 24.4%, respectively. No new cytokine release syndrome or neurologic events and no new treatment-related deaths occurred since the primary EFS analysis. The safety profile of axi-cel remained consistent with prior studies. Improved OS was associated with an increased proportion of a naive T-cell phenotype (CCR7+CD45RA+ T cells, descriptive p < 0.05) in the infused product. Conclusions: Axi-cel as second-line therapy demonstrated a significant improvement in overall survival over chemotherapy-based SOC in patients with early relapsed/refractory LBCL. Keyword: aggressive B-cell non-Hodgkin lymphoma Encore Abstract—previously submitted to ASCO 2023 Conflicts of interests pertinent to the abstract J. R. Westin Consultant or advisory role: ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Genentech, Gilead, Kite, a Gilead Company, MorphoSys/Incyte, Monte Rosa, Novartis, Umoja Research funding: ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Genentech, Gilead, Kite, a Gilead Company, MorphoSys/Incyte, Monte Rosa, Novartis O. O. Oluwole Consultant or advisory role: Pfizer, Kite, a Gilead Company, Gilead, AbbVie, Janssen, TG Therapeutics, ADC Therapeutics, Novartis, Epizyme, Curio Science, Nektar Therapeutics, Cargo Therapeutics, and Caribou Biosciences Honoraria: Kite, a Gilead Company, Pfizer, and Gilead Research funding: Kite, a Gilead Company, Pfizer, Daiichi Sankyo, and Allogene M. J. Kersten Consultant or advisory role: Bristol Myers Squibb/Celgene, Kite, a Gilead Company, Miltenyi Biotec, Novartis, Adicet Bio, and Roche Honoraria: Bristol Myers Squibb/Celgene, Kite, a Gilead Company, Miltenyi Biotec, Novartis, Adicet Bio, and Roche Research funding: Kite, Roche, Takeda, and Celgene Travel grants: Kite, Miltenyi, Novartis, and Roche D. B. Miklos Consultant or advisory role: Janssen, Adaptive Biotechnologies, Kite, a Gilead Company, Bristol Myers Squibb, and Miltenyi Honoraria: Janssen Research funding: Janssen Other remuneration: patents, royalties, other intellectual property as a cGVHD patent holder for ibrutinib as cGVHD therapy with no compensation; and travel and other support from Janssen M. A. Perales Consultant or advisory role: Cidara Therapeutics, Medigene, Sellas Life Sciences, and NexImmune Stock ownership: NexImmune, Omeros, and OrcaBio Honoraria: Adicet, Allovir, Caribou Biosciences, Celgene, Bristol Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma Research funding: Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis A. Ghobadi Consultant or advisory role: Amgen, Atara, Bristol Myers Squibb, CRISPR Therapeutics, Kite, and Wugen Inc. Honoraria: Kite, a Gilead Company Research funding: Amgen, Genentech, and Kite A. Sureda Consultant or advisory role: AbbVie, Bristol Myers Squibb/Celgene, Genmab, Janssen, Miltenyi, MSD, and Takeda Honoraria: AbbVie, Bristol Myers Squibb/Celgene, Genmab, Janssen, Kite, a Gilead Company, Novartis, MSD, and Pierre Fabre, Takeda Research funding: Takeda Travel grants: Kite and Takeda Other remuneration: speakers’ bureau participation for Takeda C. A. Jacobson Consultant or advisory role: Kite, Novartis, Bristol Myers Squibb/Celgene, Instil Bio, ImmPACT Bio, Lonza, Ipsen, Epizyme bluebird bio, and Daiichi Sankyo Honoraria: Kite, a Gilead Company, Novartis, Bristol Myers Squibb/Celgene, Instil Bio, ImmPACT Bio, Lonza, Ipsen, Epizyme, bluebird bio, and Daiichi Sankyo Research funding: Kite and Pfizer U. Farooq Consultant or advisory role: MorphoSys Honoraria: Caribou and Kite, a Gilead Company T. van Meerten Consultant or advisory role: Janssen and Kite Honoraria: Kite, a Gilead Company, Gilead Sciences, Celgene/Bristol Myers Squibb Research funding: Celgene/Bristol Myers Squibb and Genentech M. L. Ulrickson Consultant or advisory role: Gilead Sciences and Stemline M. Elsawy Consultant or advisory role: Bristol Myers Squibb, Kite, a Gilead Company, Janssen, Novartis, and Pfizer Honoraria: Bristol Myers Squibb, Kite, a Gilead Company, Janssen, Novartis, and Pfizer L. A. Leslie Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, Eli Lilly, Epizyme, Janssen/J&J, Kite, a Gilead Company, Merck, Pharmacyclics, Seagen, and TG Therapeutics Travel grants: AbbVie, AstraZeneca, BeiGene, Celgene/Bristol Myers Squibb, Eli Lilly, Epizyme, Kite, a Gilead Company, Janssen, Pharmacyclics, Seagen, and TG Therapeutics Other remuneration: speakers' bureau participation for AbbVie, AstraZeneca, BeiGene, Celgene/Bristol Myers Squibb, Eli Lilly, Epizyme, Kite, a Gilead Company, Janssen, Pharmacyclics, Seagen, and TG Therapeutics S. Chaganti Consultant or advisory role: Adicet Bio, Atara Bio, Incyte, Kite, a Gilead Company, and Orion Pharma Honoraria: Adicet Bio, Atara Bio, Incyte, Kite, a Gilead Company, and Orion Pharma Research funding: Atara Bio, Autolus, Genmab, Janssen, Kite, MorphoSys, and Novartis Travel grants: Kite, a Gilead Company, and Takeda Other remuneration: speakers’ bureau participation for Hartley Taylor, Incyte, Kite, a Gilead Company, and Takeda M. Dickinson Consultant or advisory role: Gilead Sciences, MSD, Novartis, and Roche Honoraria: Gilead Sciences, MSD, Novartis, and Roche Research funding: Novartis and Roche Other remuneration: speakers’ bureau participation for Gilead Sciences, MSD, Novartis, and Roche Y. Yang Employment or leadership position: Kite, a Gilead Company M. Schupp Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Sciences C. To Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Sciences F. L. Locke Consultant or advisory role: Allogene, Amgen, bluebird bio, Bristol Myers Squibb/Celgene, Calibr, Cellular Biomedicine Group, Cowen, ecoR1, Emerging Therapy Solutions, Gerson Lehman Group, GammaDelta Therapeutics, Iovance, Janssen, Kite, a Gilead Company, Legend Biotech, Novartis, Umoja, and Wugen Research funding: Allogene, Kite, and Novartis Other remuneration: patents, royalties, other intellectual property from several patents held by the institution in author’s name (unlicensed) in the field of cellular immunotherapy

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