FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma

FDA accelerated approval (Feb 16, 2024)

The FDA granted accelerated approval to lifileucel (Amtagvi; Iovance Biotherapeutics), a tumor-derived autologous T-cell immunotherapy, for 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.

Evidence supporting approval

Safety and efficacy were evaluated in a global, multicenter, multicohort, open-label, single-arm trial in previously treated unresectable/metastatic melanoma. Of 89 patients who received lifileucel, 2 were excluded because product did not meet specification and 5 were excluded due to product comparability.

Treatment included lymphodepletion with cyclophosphamide (60 mg/kg daily with mesna for 2 days) then fludarabine (25 mg/m² daily for 5 days), followed by lifileucel infusion and IL-2 (aldesleukin) 600,000 IU/kg every 8–12 hours for up to 6 doses.

Efficacy outcomes

Primary outcomes were ORR and DoR. In 73 patients treated within the recommended dose range (7.5×10^9 to 72×10^9 viable cells), ORR was 31.5% (95% CI: 21.1–43.4). Median DoR was not reached (95% CI: 4.1 months, NR). Median time to initial response was 1.5 months.

Safety

Prescribing information includes a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Common adverse reactions (≥20%) included chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, and dyspnea.