eligibility_summary
Adults ≥18 (ECOG 0–1) with unresectable/metastatic melanoma, measurable disease, prior 1–3 systemic regimens incl PD‑1 (and BRAF V600+ must have had BRAF±MEK), ≥1 resectable lesion ≥1.5 cm for TIL, adequate organ function, AEs ≤Grade 1, ≥28‑day washout, contraception. Exclude: other anticancer/investigational therapy, pregnant/breastfeeding, serious illness/infection, prior allograft/cell therapy, uveal melanoma, hypersensitivity, immunodeficiency, LVEF<45%/NYHA>1, FEV1≤60%, recent other cancers, symptomatic/untreated brain mets.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase II single-arm trial of lifileucel (LN-144), an autologous tumor-infiltrating lymphocyte (TIL) adoptive cell therapy, given after reduced-dose lymphodepletion with cyclophosphamide (alkylating agent) and fludarabine (purine analog antimetabolite), followed by interleukin-2 (cytokine). Mechanisms: Ex vivo–expanded patient TILs (primarily CD8+/CD4+ T cells) recognize melanoma neoantigens via their T-cell receptors and mediate direct tumor cytotoxicity. Cyclophosphamide/fludarabine deplete host lymphocytes (including regulatory/suppressive populations), reduce cytokine sinks, and create “space” to enhance TIL engraftment and expansion. IL‑2 drives T-cell proliferation/survival via IL‑2 receptor–JAK/STAT signaling. Targets/pathways: tumor cells expressing melanoma antigens/neoantigens, TCR-mediated recognition, modulation of homeostatic cytokines and the immunosuppressive milieu to favor antitumor T cells.