FDA greenlights Amtagvi: New hope for treating advanced melanoma

By Lisa Marie Basile | Fact-checked by Davi Sherman
Published February 22, 2024

Key Takeaways

  • The United States Food and Drug Administration (FDA) approved Amtagvi (lifileucel) for unresectable or metastatic melanoma patients who failed certain previous treatments. It is the first FDA-approved cellular therapy for patients with solid tumors.

  • Amtagvi was granted accelerated approval based on its Phase II clinical trial results: Among 73 adult patients treated with Amtagvi,  31.5% exhibited an objective response rate. A more extensive Phase III trial is now underway.

This week, the United States Food and Drug Administration (FDA) approved Amtagvi (lifileucel), a first-of-its-kind cellular therapy used to treat solid tumors. In this case, it’s for adult patients with melanoma.[]

Faranak Kamangar, MD, a board-certified dermatologist at Sutter Health in Palo Alto, CA, tells MDlinx that patients for whom Amtagvi might be appropriate generally have few treatment options and are looking at a poor prognosis. 

Amtagvi is approved for patients with either unresectable melanoma or metastatic melanoma previously treated with other therapies, such as a PD-1 blocking antibody or, if BRAF V600 mutation is positive, a BRAF inhibitor with or without a MEK inhibitor).  The therapy was developed by Iovance Biotherapeutics.[][]

Unresectable or metastatic melanoma are some of the most challenging cancers to treat.  While localized melanoma has a >99% 5-year survival rate, distant metastatic melanoma only has a 35% 5-year survival rate. [][]

“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,” Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research (CBER), told the FDA.[]

Kim Margolin, MD, medical oncologist and Medical Director of the Melanoma Program at Saint John’s Cancer Institute in Santa Monica, CA, tells MDLinx, “Amtagvi is not a drug; it’s a form of adopted self-therapy produced from cells of the patients who have the cancer. In this case, we call it TIL-cell therapy.”[]

“T-cell immunotherapy is the cutting edge of science; it has been done in blood cancers, but this is the first application in a solid tumor. A portion of the patient's tumor is removed, and the patient's own T cells are extracted and deployed back as an infusion to help attack the cancer cells,” Dr. Kamangar explains.

Dr. Margolin adds that patients receiving this therapy “must have a tumor that can be safely removed or biopsied in sufficient quantity (a cubed centimeter total) to provide enough tumor-infiltrating lymphocytes.” 

She says that patients receiving this therapy must also be preconditioned with high doses of lymph-depleting chemotherapy to induce the production of growth factors (homeostatic cytokines) that promote lymphocyte growth.

“When you lympho-deplete the patient, those homeostatic cytokines increase to replace those lymphocytes,” Dr. Margolin explains.

Amtagvi’s road to approval

Amtagvi was granted accelerated approval based on its Phase II clinical trial results. The global, multicenter, multicohort clinical study included 73 adult patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy.

“Effectiveness was established based on objective response rate to treatment and duration of response (measured from the date of confirmed initial objective response to the date of progression, death from any cause, starting a new anti-cancer treatment or discontinuation from follow-up, whichever came first),” the FDA clarifies.[]  

The objective response rate among the 73 patients treated with Amtagvi at the recommended dose was 31.5%. Three patients (4.1%) saw a complete response, and 20 patients (27.4%) saw a partial response. “Among patients who were responsive to the treatment, 56.5%, 47.8%, and 43.5% continued to maintain responses without tumor progression or death at six, nine, and 12 months,” the FDA reports.[] 

A larger, confirmatory Phase III trial is now underway. “We need a randomized trial, where there is a control group, to demonstrate patient benefit, ” Dr. Margolin says. “And if that study is positive, it’ll push the FDA to grant full approval.”

Dr. Margolin and Dr. Kamangar say this drug is revolutionary—and urgently necessary. “This is a real signal of hope,” says Dr. Margolin. “We talk about transformational versus incremental work [in medicine]. This is a transformational step. We’ve got something that has never been done before—never even gone to the FDA for approval—and never shown this kind of activity in patients.”

“Melanoma is unfortunately still on the rise, and it is a great disease burden in our dermatology practices, leading to morbidity and mortality,” Dr. Kamangar says. “I am very excited for the advance in therapies in this field.”

This kind of therapy may expand into other realms of cancer treatment. “TIL approaches are being explored in other types of solid tumors, including lung, head and neck and cervical cancers,” says Janice Mehnert, MD, a melanoma expert at NYU Langone’s Perlmutter Cancer Center. “The early results are promising. This is definitely a place to watch moving forward.”

What this means for you

The FDA has approved Amtagvi, a groundbreaking cellular therapy, offering new hope for patients with advanced melanoma. Accelerated approval was granted after a Phase II trial showed a 31.5% objective response rate, with a Phase III trial currently underway.

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