FDA Grants Accelerated Approval to Lifileucel for Unresectable or Metastatic Melanoma

February 16, 2024

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On February 16, 2024, the Food and Drug Administration granted accelerated approval to lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.), 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.

Full prescribing information for Amtagvi will be posted here

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 due to product comparability. Lifileucel was administered following a lymphodepleting regimen consisting of cyclophosphamide 60 mg/kg daily with mesna for 2 days followed by fludarabine 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 6 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 6.

The main efficacy outcome measures were objective response rate (ORR) and duration of response (DoR). The median time to initial response to lifileucel was 1.5 months. ORR was based on 73 subjects who received lifileucel within the recommended dosing range of 7.5 x109 to 72x109 viable cells. ORR was 31.5% (95% CI: 21.1, 43.4) and median DoR was not reached (NR) (95% CI: 4.1 months, NR).

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.

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. 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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology.