FDA Approval Summary: Lifileucel for Unresectable or Metastatic Melanoma Previously Treated with an Anti–PD-1–Based Immunotherapy

On February 16, 2024, the FDA granted accelerated approval to lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) 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 an MEK inhibitor. Lifileucel is the first tumor-derived T-cell therapy approved by the FDA. In the phase II single-arm trial, Study C-144-01, that served as the basis for approval, the objective response rate among patients treated with lifileucel within FDA-approved dose range (7.5 × 109 to 72 × 109 viable cells, n = 73) in the primary efficacy cohort was 31.5% (95% confidence interval, 21.1%-43.4%), including three (4.1%) complete responses and 20 (27.4%) partial responses. The median duration of response was not reached (95% confidence interval, 4.1 months-not reached). Among the responders (n = 23), 56.5%, 47.8%, and 43.5% maintained durable responses at 6, 9, and 12 months, respectively. Among all patients who received lifileucel (n = 156) in the primary and supportive cohorts of Study C-144-01, 95.5% of patients experienced at least one Grade 3 treatment-emergent adverse event and 87.8% experienced at least one Grade 4 treatment-emergent adverse event. Lifileucel labeling includes a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary impairment, and renal impairment.