FDA Grants Accelerated Approval to Lifileucel for Unresectable or Metastatic Melanoma

On February 16, 2024, the US Food and Drug Administration (FDA) granted accelerated approval to lifileucel for patients with unresectable or metastatic melanoma that had previously been treated with a PD-1 blocking antibody and, if BRAF V600-positive, a BRAF inhibitor with or without a MEK inhibitor.

This regulatory decision was based on results from a global, multicenter, multicohort, open-label, single arm trial. In this trial, 89 patients in this population received lifileucel with 7 patients excluded for not meeting specifications or due to product comparability. The administration of lifileucel followed a lymphodepleting regimen of cyclophosphamide with mesna for 2 days, followed by fludarabine for 5 days. Within 3 to 24 hours after infusion, patients received IL-2 (aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to 6 doses, to support cell expansion in vivo. The median lifileucel dose administered was 21.1 x 109 viable cells. The median number of administered IL-2 (aldesleukin) doses was 6. The main efficacy outcomes were objective response rate (ORR) and duration of response (DOR).

The median time to initial response to lifileucel was 1.5 months. The ORR, based on 73 patients who received the recommended dose of lifileucel (between 7.5 x 109 viable cells and 72 x 109 viable cells), was 31.5%. The median DOR was not reached. The most common adverse events, occurring in ≥20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

There is a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The recommended dose of lifileucel is 7.5 x 109 to 72 x 109 viable cells.

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FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. Published February 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma