FDA Approves Amtagvi, the First TIL Therapy for a Solid Tumor

The FDA has granted accelerated approval for Amtagvi (lifileucel) to treat patients with advanced melanoma. Developed by Iovance Biotherapeutics, Amtagvi is the first approved tumor-infiltrating lymphocyte (TIL) therapy designed for patients with advanced melanoma who have experienced progression after previous treatment. It is indicated for those patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor.

Amtagvi is a one-time therapy intended that requires a patient’s cancer-fighting cells to be collected so they can be used to manufacture an individualized treatment.

Melanoma is a type of skin cancer involving the uncontrolled growth of pigment-producing cells. It is one of the most aggressive and therapy-resistant types of cancer. According to estimates from the American Cancer Society, more than 100,000 new melanomas will be diagnosed in the United States this year, with about 8,200 deaths expected from melanoma.

The wholesale acquisition cost of Amtagvi will be $515,000, Iovance executives said during an investor call. Executives said that three-quarters of advanced melanoma patients are currently insured through commercial plans, Medicare Advantage plans and Medicare IPPS exempt plans. Iovance executives expect to have coverage similar to CAR T therapies, requiring prior authorization with coverage consistent with the label.

Authorized treatment centers will administer Amtagvi to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose Proleukin (aldesleukin), which is Iovance acquired in May 2023. Proleukin is used to treat patients with metastatic renal cell carcinoma and melanoma. Proleukin is used to help promote T cell growth in the body.

More than 30 centers are already available to collect and ship tumor tissues to the Iovance Cell Therapy Center site for manufacturing. Additional treatment centers are finishing the onboarding process, and executives said they expect to have a total of 50 centers available to provide treatment by the end of the month.

Iovance has a support program available, called IovanceCares, that will assist patients and physicians with reimbursement, financial support and a case manager for patients,

The FDA approval is based on safety and efficacy results from the C-144-01 clinical trial, which enrolled patients with advanced melanoma previously treated with anti-PD-1 therapy and targeted therapy. The primary efficacy analysis set included 73 patients from Cohort 4; 31.5% achieved an objective response with a median duration of response not reached at 18.6 months follow-up. Additionally, the supporting pooled efficacy set included a total of 153 patients from Cohort 4 and Cohort 2. Among these patients, 31.4% achieved an objective response with a median duration of response not reached at 21.5 months follow-up.

Iovance is conducting a phase 3 confirmatory trial, TILVANCE-301, and also is conducting trials of Amtagvi in solid tumor types.

Amtagvi has a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Warnings and precautions include treatment-related mortality, prolonged severe cytopenia, internal organ hemorrhage, severe infection, cardiac disorder, respiratory failure, acute renal failure, and hypersensitivity reactions.