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Soo Park, MD


FDA Grants Accelerated Approval to Cellular Therapy for Unresectable or Metastatic Melanoma

By: JNCCN 360 Staff
Posted: Tuesday, February 20, 2024

On February 16, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to lifileucel (Amtagvi), a tumor-derived autologous T-cell immunotherapy, for adults with unresectable or metastatic melanoma previously treated with a PD-1–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without a MEK inhibitor.

Safety and efficacy were evaluated in a global, multicenter, multicohort, open-label, single-arm trial in patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1–blocking antibody, and if BRAF V600 mutation–positive, a BRAF inhibitor with or without a MEK inhibitor. Among 89 patients who received lifileucel, two patients were excluded because the product did not meet specification, and five patients were excluded because of product comparability.

Lifileucel was administered after a lymphodepleting regimen consisting of cyclophosphamide (60 mg/kg daily) with mesna for 2 days followed by fludarabine (5 mg/m2 daily) for 5 days. Between 3 to 24 hours after infusion, patients received interleukin-2 (IL-2; aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to six doses to support cell expansion in vivo. The median administered lifileucel dose was 21.1 × 109 viable cells. The median number of administered IL-2 doses was six.

The main efficacy outcome measures were objective response rate and duration of response. The median time to initial response to lifileucel was 1.5 months. Objective response rate was based on 73 subjects who received lifileucel within the recommended dosing range of 7.5 x 109 to 72 x 109 viable cells. Objective response rate was 31.5% (95% confidence interval [CI] = 21.1%–43.4%), and median duration of response was not reached (95% CI = 4.1 months to not reached).

The prescribing information contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions (≥ 20%) in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea. The recommended lifileucel dose is 7.5 x 109 to 72 x 109 viable cells.

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