Accelerated Approval Given to Lifileucel in Metastatic Melanoma

Data from the multicenter, multicohort, open-label, single-arm C-144-01 trial supported the FDA approval of lifileucel as a treatment for adult patients with unresectable or metastatic melanoma.

Lifileucel (Amtagvi) has been granted accelerated approval by the FDA for patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, according to a press release from the FDA.¹

If patients are BRAF V600 positive and have received prior treatment with a BRAF inhibitor with or without a MEK inhibitor, they may receive lifileucel. Lifileucel is a tumor-derived autologous T-cell therapy.

Supporting results for the approval came from the phase 2 C-144-01 trial. The median time to initial response was 1.5 months. A total of 73 patients were evaluated for objective responses. These patients were given lifileucel at 7.5 x 10⁹ to 72 x 10⁹ viable cells. The objective response rate was 31.5% (95% CI, 21.1%-43.4%), and the median duration of response was not reached (95% CI, 4.1 months-not reached).

Overall, 89 patients received treatment, and 7 were excluded. Patients were given a lymphodepleting regimen of lifileucel beginning with cyclophosphamide at 60 mg/kg daily with mesna for 2 days followed by fludarabine at 25 mg/m² daily for 5 days. Starting at 3 to 24 hours after infusion, patients could receive IL-2 at 600,000 IU/kg every 8 to 12 hours for a maximum of 6 doses to support cell expansion in vivo. Patients received a median dose of 21.1× 10⁹ viable cells, and the median number of IL-2 doses was 6.

The boxed warning highlights treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal implant. Patients most commonly experienced chills, pyrexia, fatigue, and tachycardia.

In May 2023, a biologics license application was given for lifileucel in this indication, with the original prescription drug user fee act being November 25, 2023.²

At the time of the updated clinical trial analysis for C-144-01, lead trial investigator Amod Sarnaik, MD, professor of Cutaneous Oncology and Immunology at H. Lee Moffitt Cancer Center, said, “The trial demonstrated a robust and clinically meaningful response rate and long-term durability following one-time treatment. We hope to offer lifileucel to many more patients after initial progression on [ICIs].”³

References

1. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. https://shorturl.at/cgC48
2. Iovance Biotherapeutics announces U.S. Food and Drug administration acceptance of the biologics license application of lifileucel for the treatment of advanced melanoma. News release. Iovance Biotherapeutics, Inc. May 26, 2023. Accessed February 16, 2024. bit.ly/3OOSHLA
3. Iovance Biotherapeutics announces updated clinical data for lifileucel in advanced melanoma at Society for Immunotherapy of Cancer (SITC) Annual Meeting. News release. Iovance Biotherapeutics, Inc. November 10, 2022. Accessed February 16, 2024. bit.ly/3WFuBEW