Iovance’s AMTAGVI (lifileucel) gets US FDA accelerated approval for advanced melanoma

Iovance Biotherapeutics has received US Food and Drug Administration (FDA) approval for AMTAGVI (lifileucel) suspension for intravenous infusion. AMTAGVI is a tumour-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This indication is approved under an accelerated approval based on overall response rate (ORR) and duration of response. Iovance is also conducting TILVANCE-301, a Phase 3 trial to confirm clinical benefit.

AMTAGVI is the first and the only one-time, individualised T cell therapy to receive FDA approval for a solid tumor cancer. The proposed mechanism for AMTAGVI offers a new cell therapy approach that deploys patient-specific T cells called TIL cells. When cancer is detected, the immune system creates TIL cells to locate, attack, and destroy cancer. TIL cells recognise distinctive tumour markers on the cell surface of each person’s cancer. When cancer develops and prevails, the body’s natural TIL cells can no longer perform their intended function to fight cancer.

AMTAGVI is manufactured using a proprietary process to collect and expand a patient’s unique T cells from a portion of their tumor. AMTAGVI returns billions of the patient’s T cells back to the body to fight their cancer.* Authorised Treatment Centers (ATCs) will administer AMTAGVI to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose PROLEUKIN (aldesleukin).

The FDA approval is based on safety and efficacy results from the C-144-01 clinical trial. C-144-01 is a global, multicenter trial investigating AMTAGVI in patients with advanced melanoma previously treated with anti-PD-1 therapy and targeted therapy, where applicable. AMTAGVI demonstrated deep and durable responses. The primary efficacy analysis set included 73 patients from Cohort 4 who received the recommended AMTAGVI dose from an approved manufacturing facility. Among the 73 patients, 31.5% achieved an objective response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with a median duration of response not reached at 18.6 months follow-up² (43.5% of responses had a duration greater than 12 months). Additionally, the supporting pooled efficacy set included a total of 153 patients from Cohort 4 and Cohort 2. Among the 153 patients, 31.4% achieved an objective response by RECIST 1.1 with a median duration of response not reached at 21.5 months follow-up² (54.2% of responses had a duration greater than 12 months). The detailed results of clinical trial C-144-01 are published in The Journal for ImmunoTherapy of Cancer (Chesney 2022).