Today, the U.S. Food and Drug Administration approved Amtagvi, the first cellular therapy indicated for the treatment of adult patients with a type of skin cancer (melanoma) that is unable to be removed with surgery (unresectable) or has spread to other parts of the body (metastatic) that previously has been treated with other therapies (a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor).

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “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.”

Melanoma is a form of skin cancer that is often caused by exposure to ultraviolet light, which can come from sunlight or indoor tanning. Although melanomas only represent approximately 1% of all skin cancers, they account for a significant number of cancer-related deaths. Melanoma can spread to other parts of the body if not detected and treated early, resulting in metastatic disease.

Treatment for unresectable or metastatic melanoma may include immunotherapy using PD-1 inhibitors, which are antibodies targeting certain proteins in the body to help the immune system fight off cancer cells. In addition, drugs targeting the BRAF gene, which helps with managing the growth and functioning of cells, may be used for treating melanoma associated with BRAF gene mutations. Those patients whose melanoma has progressed with these therapies have a high unmet medical need.

Amtagvi is a tumor-derived autologous T cell immunotherapy composed of a patient’s own T cells, a type of cell that helps the immune system fight cancer. A portion of the patient’s tumor tissue is removed during a surgical procedure prior to treatment. The patients’ T cells are separated from the tumor tissue, further manufactured and then returned to the same patient as a single dose for infusion. This is the first FDA-approved tumor-derived T cell immunotherapy.

“Melanoma is a life-threatening cancer that can cause devastating impacts to affected individuals, with a significant risk of metastasizing and spreading to other areas in the body,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. “Today’s approval reflects the FDA’s dedication and commitment to the development of innovative, safe and effective treatment options for cancer patients.”

Amtagvi was approved through the Accelerated Approval pathway, under which the FDA may approve drugs for serious or life-threatening illnesses or conditions where there is an unmet medical need and the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients (improving how patients feel or function, or whether they survive longer). This pathway generally gives patients the opportunity for earlier access to a promising therapy while the company conducts further trials to verify the predicted clinical benefit. A confirmatory trial is ongoing to verify Amtagvi’s clinical benefit.

The safety and effectiveness of Amtagvi was evaluated in a global, multicenter, multicohort clinical study including adult patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1 blocking antibody, and if positive for the BRAF V600 mutation, a BRAF inhibitor or BRAF inhibitor with an MEK inhibitor. 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). Among the 73 patients treated with Amtagvi at the recommended dose, the objective response rate was 31.5%, including three (4.1%) patients with a complete response and 20 (27.4%) patients with 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, respectively.

Patients treated with Amtagvi may exhibit prolonged severe low blood count, severe infection, cardiac disorder, or develop worsened respiratory or renal function or have fatal treatment-related complications. A Boxed Warning is included in the label containing information about these risks. Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated.

The most common adverse reactions associated with Amtagvi included chills, fever, fatigue, tachycardia (abnormally fast heart rate), diarrhea, febrile neutropenia (fever associated with a low level of certain white blood cells), edema (swelling due to buildup of fluid in body tissues), rash, hypotension, hair loss, infection, hypoxia (abnormally low oxygen levels in the body) and feeling short of breath.

Amtagvi also received Orphan Drug, Regenerative Medicine Advanced Therapy, Fast Track, and Priority Review designations.

The FDA granted the approval of Amtagvi to Iovance Biotherapeutics Inc.

https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma