FDA Approves Lifileucel for Unresectable or Metastatic Melanoma


The FDA has approved lifileucel suspension (Amtagvi) for adult patients with unresectable or metastatic melanoma following prior treatment with a PD-1 inhibitor, and if BRAF V600 mutation positive, a BRAF inhibitor, with or without a MEK inhibitor.



The FDA has granted accelerated approval to lifileucel (Amtagvi) for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor.

The decision is supported by data from the phase 2 C-144-01 trial (NCT02360579), which showed that in those who received the recommended dose (n = 73), the objective response rate (ORR) was 31.5% (95% CI, 21.1%-43.4%); this included a complete response rate of 4.1% and a partial response rate of 27.4%.

Of those who responded, 56.5%, 47.8%, and 43.5% continued to respond without tumor progression or death at 6, 9, and 12 months, respectively. The median duration of response (DOR) had not been reached (NR; 95% CI, 4.1 months-NR). The median time to initial response to the therapy was 1.5 months.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated in a press release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

About C-144-01

The global, multicenter, multicohort, open-label, single-arm trial enrolled patients who were at least 18 years of age and who had unresectable or metastatic melanoma that was stage IIIC or stage IV by the American Joint Committee on Cancer v.7. They were required to have experienced radiologic disease progression and must have progressed on at least 1 previous systemic therapy, including a PD-L1 antibody, and if they had BRAF V600E mutation–positive disease, a BRAF or BRAF/MEK inhibitor.

They needed to have an ECOG performance status of 0 or 1, an estimated life expectancy of at least 3 months, at least 1 resectable lesion, and acceptable hematologic parameters and organ function.

Following a lymphodepleting regimen comprised of 60 mg/kg of cyclophosphamide daily with mesna for 2 days followed by 25 mg/m2 of fludarabine daily for 5 days, lifileucel was administered. Three to 24 hours following infusion, patients were given 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 given was 21.1 × 109 viable cells. The median number of administered doses of aldesleukin was 6.

The main efficacy outcome measures included ORR and DOR.


The prescribing information for the therapy contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment, according to the FDA.

The most common adverse reactions reported in at least 20% of patients included chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.


  1. FDA approves first cellular therapy to treat patients with unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma
  2. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. FDA. February 16, 2024. Accessed February 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma
  3. Iovance's Amtagvi (lifileucel) receives US FDA accelerated approval for advanced melanoma. News release. Iovance Biotherapeutics, Inc. February 16, 2024. Accessed February 16, 2024. https://ir.iovance.com/news-releases/news-release-details/iovances-amtagvitm-lifileucel-receives-us-fda-accelerated
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