Lisocabtagene maraleucel is a CD19-directed genetically modified autologous cellular immunotherapy administered as a defined composition to reduce variability in CD8+ and CD4+ T-cell dose. The CAR is comprised of a murine FMC63 monoclonal antibody-derived single chain variable fragment (scFv), IgG4 hinge region, CD28 transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3 zeta activation domain. CD3 zeta signalling is critical for initiating T-cell activation and antitumor activity, while 4-1BB (CD137) signalling enhances the expansion and persistence of lisocabtagene maraleucel.
CAR binding to CD19 expressed on the cell surface of tumour and normal B cells induces activation and proliferation of CAR T cells, release of pro-inflammatory cytokines, and cytotoxic killing of target cells.
In TRANSCEND, following infusion, lisocabtagene maraleucel exhibited an initial expansion followed by a biexponential decline. The median time of maximal expansion in peripheral blood occurred 11 days after the first infusion. Lisocabtagene maraleucel was present in peripheral blood for up to 2 years.
Responders (N=150) had a 2.85-fold higher median Cmax than nonresponders (N=45) (33,766.0 vs. 11,846.0 copies/µg). Responders had a 2.22-fold higher median AUC0-28d than nonresponders (257,769.0 vs. 116,237.3 day*copies/µg).
Patients <65 years old (N=145) had a 2.93-fold and 2.35-fold higher median Cmax and AUC0-28d, respectively, compared to patients ≥65 years old (N=102, including 77 patients with age 65-74 years, 24 with age 75-84 years, and 1 with age ≥85 years). Sex and body weight did not show clear relationships to Cmax and AUC0-28d.
Genotoxicity assays and carcinogenicity studies were not conducted.
In vitro expansion studies from healthy donors and patients showed no evidence for transformation and/or immortalization and no preferential integration near genes of concern in lisocabtagene maraleucel T cells.
Given the nature of the product, non-clinical studies on fertility, reproduction and development were not conducted.
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