FDA Accepts BLA for Lifileucel for Difficult-to-Treat Melanoma

According to estimates from the American Cancer Society, more than 97,000 new melanomas will be diagnosed in the United States this year, with close to 8,000 deaths expected from melanoma.

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Iovance Biotherapeutics recently announced that the FDA has accepted its Biologics License Application (BLA) for lifileucel and has granted Priority Review Status. Lifileucel is an individualized, one-time cell therapy intended for patients with advanced melanoma. The target date for a decision is set for November 25, 2023. After a preliminary review, the FDA does not currently have any plans to hold an advisory committee meeting to discuss the BLA application for lifileucel and has not identified any potential review issues.

Lifileucel is a polyclonal tumor infiltrating lymphocyte (TIL) therapy designed for patients with advanced melanoma who have experienced progression after previous treatment with anti-PD-1/L1 therapy and targeted therapy. TIL therapies utilize the immune system’s ability to recognize and destroy cancer cells. If approved, lifileucel will become the first FDA-approved therapy for this specific treatment setting.

“The BLA acceptance is a significant milestone in our mission to deliver lifileucel as the first individualized, one-time cell therapy for a solid tumor,” Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, said in a statement. “The FDA’s commitment to a six-month Priority Review validates the unmet need and urgency for new treatment options for patients with advanced melanoma who have progressed on or after standard of care therapies.”

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 97,000 new melanomas will be diagnosed in the United States this year, with close to 8,000 deaths expected from melanoma.

In the last decade, immune checkpoint inhibitors and targeted therapies have majorly improved treatment outcomes in advanced melanoma. However, a substantial percentage of patients do not respond or eventually relapse, and treatment options are limited after progression.

The BLA submission is supported by the Phase II C-144-01 trial, in which an independent review committee assessed outcomes of 153 melanoma patients treated with lifileucel in a multicenter cell therapy study. At baseline, participants had high disease burden and had received three lines of prior therapy. The Overall Response Rate (ORR), which indicates the proportion of patients who experienced a response, was 31.4% with a 95% Confidence Interval (CI) of 24.1% to 39.4%, with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival was 13.9 months and progression-free survival was 4.1 months. In terms of safety, the most common adverse effects (≥30%) were thrombocytopenia, anemia, and febrile neutropenia.

The FDA previously granted lifileucel a Regenerative Medicine Advanced Therapy (RMAT) designation for advanced melanoma. A drug is eligible for RMAT designation if it is a regenerative medicine therapy (e.g., cell therapy, therapeutic tissue engineering product, or human cell and tissue product) intended to treat a serious or life-threatening condition and preliminary evidence suggests that the drug has the potential to address unmet medical needs for the disease.