Tumor infiltrating lymphocyte (TIL) therapy, first pioneered by Dr. Stephen Rosenberg from the National Cancer Institute, isolates immune cells called lymphocytes from a patient’s surgically removed tumor that are then grown in large quantities in the lab. The army of grown TILs are then reinfused back into the patient where they recognize and destroy cancer cells in the body. Prior to the reinfusion, the patient is treated with chemotherapy to deplete all existing lymphocytes. After TIL reinfusion, the patient is treated with a therapy that encourages lymphocytes in the body to grow and divide.
Iovance Biotherapeutics has a proprietary TIL manufacturing process that is being used to develop an individualized TIL therapy called Lifileucel. It is being tested in advanced unresectable or metastatic melanoma patients who have progressed on or after treatment with checkpoint immunotherapy and/or BRAF/MEK targeted therapy. Recent data presented at the Society for Immunotherapy of Cancer (SITC) annual conference demonstrated durable efficacy and a 4-year overall survival rate of 21.9% in this advanced and difficult to treat patient population.3
Included in the above study is a small group of patients with mucosal melanoma, a rare melanoma subtype that develops in the mucous membranes of the body. Mucosal melanoma accounts for only 1% of all melanomas diagnosed and represents a difficult to treat subtype of the disease. Preliminary data was presented by Dr. Evido Domingo-Musibay (Masonic Cancer Center) at the 2023 European Society of Medical Oncology Annual Congress and by Dr. Harriet Kluger (Yale Cancer Center) at this year’s Society for Melanoma Research Annual Congress from 12 patients with advanced mucosal melanoma that were refractory to anti-PD1 treatment. These patients had an overall response rate of 50% (6 out of 12 patients) with durable responses in 4 patients from a single infusion of Lifileucel.4 Researchers plan to follow these patients for a number of years to look at the true durability of response.
On March 24th, 2023, Iovance submitted a Biologics License Application (BLA) to the FDA for the approval of Lifileucel. The FDA decision is expected by the end of February 2024.
In addition, a large phase 3 clinical trial is now enrolling patients with untreated melanoma in a study testing the efficacy and safety of lifileucel in combination with pembrolizumab compared with pembrolizumab alone (NCT05727904).