Lifileucel

Lifileucel is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. The specific mechanism of action of lifileucel is unknown.

Pharmacodynamic activity was evaluated by measuring longitudinal changes of cytokines and chemokines (IL-15, IL-6, IL-7, IL-9, IL-10, IL-12(p40), CCL2, CXCL10, IFN-γ, and TNF-α) using plasma samples collected at baseline and post-infusion of lifileucel up to Month 3. The mean level of IL-15 and CXCL10 peaked following lymphodepletion and administration of lifileucel at Day 1-4, decreased over time, and returned to baseline levels within 1-3 months. The mean IFN-γ level was below baseline post lymphodepletion and lifileucel infusion at Day 1-4 and returned to baseline by Day 14. Other cytokines and chemokines listed above did not show any noticeable changes. No difference was observed in the cytokines and chemokines level between responding and non-responding patients.

The proportion of unique TCR clonotypes from the lifileucel lots contributing to the peripheral blood TCR repertoire among infused patients was analyzed using a semi-quantitative polymerase chain reaction followed by next generation sequencing. The proportion of TCR clones that are composed of clonotypes identified in the product increases from a mean of 16% (n=125) at pre-infusion to 83% at Day 4 after lifileucel infusion. The TCR clones declined to 51% at Day 14 (n=51) and remain 37% to 41% from Day 42 (n=120) to month 12 (n=37) post-infusion of lifileucel. No significant correlation was found between lifileucel persistence and efficacy.