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Lifileucel Granted Accelerated Approval for Unresectable or Metastatic Melanoma

Melanoma.

The FDA has granted accelerated approval to lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) for adult patients with unresectable or metastatic melanoma previously treated with a programmed cell death protein 1 (PD-1) blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without a mitogen-activated protein kinase (MEK) inhibitor. Lifileucel is a tumor-derived autologous T-cell immunotherapy and is the first cellular therapy to receive an approval for solid tumors.  

Why it matters: "The FDA approval of lifileucel for the treatment of metastatic and unresectable melanoma is a momentous advancement in that it is the first cellular therapy to receive regulatory approval for solid tumors," said Matthew Hadfield, DO, a Hematology/Oncology Fellow at Brown University/Legoretta Cancer Center. "This approval was based on the C-144-01 trial, which demonstrated that 43% of pre-treated patients had responses lasting over 12 months, representing a novel therapeutic option for patients that previously had very little to control their disease."

Matthew Hadfield, DO

What they studied: The open-label, single-arm, multicohort, multicenter C-144-01 trial (NCT02360579) enrolled 89 patients with unresectable or metastatic melanoma. Key inclusion criteria required that patients 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. Patients were administered lifileucel following a lymphodepleting regimen consisting of 60 mg/kg of cyclophosphamide daily with mesna for two days, followed by 25 mg/m2 of fludarabine daily for five days. Lifileucel was administered at a median dose of 21.1x109 viable cells. As well, three to 24 hours after infusion, patients received a median of six IL-2 (aldesleukin) doses at 600,000 IU/kg every eight to 12 hours for up to six doses in order to support cell expansion in vivo.

It is noted that of the 89 patients enrolled, two patients were excluded because the product did not meet specification, and five patients were excluded due to product comparability.

The efficacy end points studied were objective response rate and duration of response.

What they found: Lifileucel produced a median time to initial response of 1.5 months. The objective response rate, which was based on 73 patients who received lifileucel at the recommended dosing range of 7.5x109 to 72x109 viable cells, was 31.5%. The median duration of response was not reached.

Adverse events: The most common adverse events experienced by ≥20% of patients receiving lifileucel in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, and dyspnea.

Additionally, the prescribing information contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. 

Conclusion: "This approval builds on decades of research, and lifileucel now has been proven to be a viable therapeutic option in solid tumor patients, concluded Dr. Hadfield. "Future combinations with existing immunotherapeutic strategies will hopefully open up entire new avenues of treatments for patients."

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