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Zevorcabtagene autoleucel (泽沃基奥仑赛注射液) is a fully humanised B cell maturation antigen (BCMA)-targeting specific chimeric antigen receptor (CAR) T-cell therapy being developed by CARsgen for the treatment of multiple myeloma. Zevorcabtagene autoleucel is an autologous CAR T cell comprising a fully human BCMA-specific scFv (25C2), a CD8α hinge region and transmembrane domain, a 4-1BB costimulatory domain and a CD3-ζ T cell activation domain. Zevorcabtagene autoleucel recognizes and induces selective toxicity against BCMA-expressing tumour cells leading to their elimination. In February 2024, zevorcabtagene autoleucel received its first approval in China for the treatment of adults with relapsed or refractory multiple myeloma who have progressed after ≥ 3 prior lines of therapy (including ≥ 1 proteasome inhibitor and an immunomodulatory agent). Clinical studies of zevorcabtagene autoleucel are underway in Canada and the US. This article summarizes the milestones in the development of zevorcabtagene autoleucel leading to this first approval for relapsed or refractory multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: Novel therapies often fail to reach the bedside due to low trial recruitment rates. Prior to conducting one of the first chimeric antigen receptor (CAR) T cell therapy trials in Canada, we used the Theoretical Domains Framework, a novel tool for identifying barriers and enablers to behavior change, to identify physician-related barriers and enablers to screening and recruiting patients for an early phase immunotherapy trial.Methods: We conducted interviews with hematologists across Canada and used a directed content analysis to identify relevant domains reflecting the key factors that may affect screening and recruitment.Results: In total, we interviewed 15 hematologists. Physicians expressed "cautious hope"; while expressing safety, feasibility, and screening criteria concerns, 14 out of 15 hematologists intended to screen for the trial (domains: knowledge, goals, beliefs about consequences, intentions). Physicians underscored the "challenging contexts," identifying resources, workload, forgetting, and patient wait times to receive CAR T cells as key practical barriers to screening (domains: environmental context and resources, memory, attention and decision-making, behavioral regulation). They also highlighted "variability in roles and procedures" that may lead to missed trial candidates (domain: social and professional role). Left unaddressed, these barriers may undermine trial recruitment.Conclusions: This study is among the first to use the Theoretical Domains Framework from the physician perspective to identify recruitment challenges to early phase trials and demonstrates the value of this approach for identifying barriers to screening and recruitment that may not otherwise have been elicited. This approach can optimize trial procedures and may serve to inform future promising early phase cancer therapy trials.Trial Registration: ClinicalTrials.gov Identifier: NCT03765177 . Registered on December 5, 2018. [ABSTRACT FROM AUTHOR]