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

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.