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 adult patients 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.

FDA update

Safety and efficacy were evaluated in a global, multicenter, multicohort, open-label, single-arm trial in patients with unresectable or metastatic melanoma who had been treated with at least one systemic therapy, including a PD-1 blocking antibody and, if positive for a BRAF V600 variant, a BRAF inhibitor with or without a MEK inhibitor. The main efficacy outcome measures were objective response rate (ORR) and duration of response (DoR).

Participants received lifileucel following a lymphodepleting regimen consisting of cyclophosphamide 60 mg/kg daily with mesna for two days followed by fludarabine 25 mg/m2 daily for five days. Three to 24 hours after infusion, patients received interleukin-2 (IL-2) at 600,000 IU/kg every 8–12 hours for up to six doses to support cell expansion in vivo. The median lifileucel dose was 21.1 × 109 viable cells. The median number of IL-2 doses was six.

The median time to initial response with lifileucel was 1.5 months. ORR was based on 73 subjects who received lifileucel within the recommended dosing range of 7.5–72 x 109 viable cells. ORR was 31.5% (95% CI = 21.1, 43.4) and median DoR was not reached (95% CI = 4.1 months, 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 reported in at least 20% of patients in the clinical trial, 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 77.5–72 x 109 viable cells. Full prescribing information for lifileucel will be posted here.

FDA’s review used Assessment Aid, a voluntary submission from the applicant to facilitate the agency’s assessment. FDA granted the application priority review and fast-track, regenerative medicine advanced therapy, and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.