Dr Kluger on the FDA Approval of Lifileucel in Advanced Melanoma

Harriet Kluger, MD, Harvey and Kate Cushing Professor of Medicine (Oncology) and of Dermatology; director, Yale SPORE in Skin Cancer; vice chair, Translational Research, Internal Medicine; chief, Division of Skin and Kidney Cancer; associate cancer center director, Education, Training and Faculty Development; deputy section chief, Medical Oncology, Yale Cancer Center, discusses the significance of the FDA approval of the tumor infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for patients with advanced melanoma.

On February 16, 2024, the FDA approved lifileucel for the treatment of adult patients with unresectable or metastatic melanoma whose disease has been previously treated with a PD-1 inhibitor, as well as a BRAF inhibitor with or without a MEK inhibitor for BRAF V600–mutated disease This regulatory decision was supported by findings from cohorts 2 and 4 of the phase 2 C-144-01 trial (NCT02360579). Patients who received lifileucel at the recommended dose (n = 73) achieved an overall response rate of 31.5%, including complete response and partial response rates of 4.1% and 27.4%, respectively.

This FDA approval is important because it marks the first cellular and TIL therapy product to be approved by the FDA for patients with solid tumors, Kluger says. Unlike CAR T-cell products, which have been used in patients with liquid tumors, TIL products use cells from patients’ tumors that will theoretically recognize multiple tumor antigens, Kluger explains. TILs are expanded, then reinfused into patients, which is different from the process of administering CAR T-cell therapy, wherein T cells are leukapheresed, engineered into CAR T-cells, then reinfused into patients, Kluger notes.

The use of TILs for the treatment of patients with solid tumors is a unique treatment paradigm, and lifileucel is likely the first of several TIL products that will be available for patients with melanoma, as well as those with other solid tumors, according to Kluger. As science and cell engineering technology becomes more sophisticated, increasingly targeted cell therapy products will emerge that will be better equipped against tumor cells than the bystander antigens present in patients’ bodies, Kluger concludes.