On February 16, the U.S. Food and Drug Administration (FDA) granted accelerated approval to lifileucel (Amtagvi), a tumor-derived autologous T-cell immunotherapy, for adult patients with unresectable or metastatic melanoma who were previously treated with a PD-1 blocking antibody, or, if they have BRAF V600 mutation–positive disease, a BRAF inhibitor with or without a MEK inhibitor.
C-144-01 Trial
Safety and efficacy were evaluated in the global, multicenter, multicohort, open-label, single-arm C-144-01 trial (ClinicalTrials.gov identifier NCT02360579) in previously treated 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, 2 patients were excluded because the product did not meet specification, and 5 patients were excluded due to product comparability.
Lifileucel was administered following a lymphodepleting regimen consisting of cyclophosphamide at 60 mg/kg daily with mesna for 2 days followed by fludarabine at 25 mg/m2 daily for 5 days. Three to 24 hours after infusion, patients received IL-2 (aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to six doses in order to support cell expansion in vivo. The median administered lifileucel dose was 21.1 × 109 viable cells. The median number of administered IL-2 (aldesleukin) 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 for lifileucel contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions (occurring in ≥ 20% of patients) 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Fast Track designation, Regenerative Medicine Advanced Therapy designation, and Orphan Drug designation.
