Iovance Biotherapeutics, Inc., a biotechnology company developing polyclonal tumor infiltrating lymphocyte (TIL) cell therapies for cancer, received approval from the U.S. FDA for AMTAGVI (lifileucel) suspension for intravenous infusion. AMTAGVI is a tumor-derived autologous T cell immunotherapy for the treatment of adults 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, individualized 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. 
 
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. 
 
The FDA approval is based on results from the C-144-01 clinical trial, a global, multicenter trial investigating AMTAGVI in patients with advanced melanoma previously treated with anti-PD-1 therapy and targeted therapy. The primary efficacy analysis included 73 patients who received the recommended AMTAGVI dose. Among the 73 patients, 31.5% achieved an objective response by Response Evaluation Criteria in Solid Tumors with a median duration of response not reached at 18.6 months follow-up (43.5% of responses had a duration greater than 12 months). 
 
Additionally, the supporting pooled efficacy set included a total of 153 patients, among which 31.4% achieved an objective response with a median duration of response not reached at 21.5 months follow-up (54.2% of responses had a duration greater than 12 months). 
 
AMTAGVI has a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. 

Manufacture of AMTAGVI

AMTAGVI will be manufactured in Philadelphia at the Iovance Cell Therapy Center (iCTC), with capacity for up to several thousand patients annually, including a nearby contract manufacturer, WuXi Advanced Therapies. Additional expansion at iCTC is underway to significantly increase this capacity over the next few years. iCTC is the first FDA-approved, centralized, and scalable manufacturing facility dedicated to producing TIL cell therapies for patients with solid tumors. AMTAGVI must be administered in an ATC, and more than 30 ATCs are prepared to collect and ship tumor tissue from patients for AMTAGVI manufacturing.
 
WuXi Advanced Therapies, a wholly owned subsidiary of WuXi AppTec, received approval from the FDA for its Philadelphia site to begin the analytical testing and manufacturing of AMTAGVI for Iovance.
 
WuXi ATU’s Philadelphia site becomes the first U.S. external manufacturing site and the first third-party contract testing, development, and manufacturing organization (CTDMO) to be approved by the FDA to support the commercial manufacturing and release of an individualized T cell therapy for a solid tumor cancer.
 
Iovance is headquartered in San Carlos, CA with an FDA-approved built-to-suit custom manufacturing facility, the Iovance Cell Therapy Center (iCTC), adjacent to WuXi ATU in the Navy Yard in Philadelphia.

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