Iovance Biotherapeutics’ Amtagvi has been introduced as the first FDA-approved T-cell immunotherapy for a solid tumor, employing a polyclonal tumor infiltrating lymphocyte (TIL) cell therapy. The personalized one-time cellular therapy is indicated for the treatment of adult patients with unresectable or metastatic melanoma who have previously received standard of care front-line PD-1 therapy and targeted therapy with a proto-oncogene B-Raf (BRAF) or BRAF/mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, if BRAF-V600 mutation is positive. With its first-to-market advantage, Amtagvi is poised to gain a major share in melanoma treatment, according to GlobalData, a leading data and analytics company.

Jasminemay Barcelon, Oncology & Hematology Analyst at GlobalData comments: “Amtagvi represents a significant improvement in the treatment of advanced melanoma, particularly for the post-immune checkpoint inhibitor patient population. It is an autologous cell therapy that involves extracting immune cells from the patient’s tumor, expanding them ex vivo, and reinfusing them into the patient. This results in enhancing the patient’s immune response to recognize tumor-specific antigens, which may be necessary to elicit a response in solid tumors characterized by a high mutational burden. In contrast to chimeric antigen receptor (CAR)-T therapies, modification of the cells is not required, but patients do undergo a similar lymphodepletion regimen before cell infusion.”

The accelerated approval for Amtagvi was supported by the results of the Phase II C-144-01 clinical trial. Efficacy analysis showed that patients who received the recommended dose had an overall response rate of 31.5%, including a 4.1% complete response rate and a 27.4% partial response rate. The median duration of response was not reached at the 18.6 month follow-up. However, 43.5% of responses had a duration greater than 12 months. In terms of safety, the label contains an IL2-driven boxed warning. Iovance has an ongoing, larger Phase III TILVANCE-301 trial of Amtagvi in combination with Keytruda versus Keytruda alone to confirm clinical benefit.

Barcelon adds: “GlobalData analyst consensus forecast projects Amtagvi to have linear growth and is expected to reach $846 million in sales by 2029, with a blockbuster potential by 2030. However, this number could be even higher following the accelerated approval due to multiple factors. GlobalData anticipates its price tag to be around $500k in the US, comparable to other cell therapies such as CAR-T cell products.”

Iovance is also preparing to file for approval in Europe, resulting in expansion into other markets. The company’s pipeline also contains potential label expansions to other solid tumors with ongoing investigations of Amtagvi as a monotherapy in cervical cancer and in combination with immune checkpoint inhibitors for melanoma, cervical, and non-small cell lung cancer (NSCLC), as well as a similar TIL therapy, LN-145, in head and neck cancer and NSCLC.

Barcelon concludes: “Amtagvi could encounter challenges in manufacturing as TILs are derived from tumor tissue rather than blood, making access slightly more challenging. TILs also exhibit high patient variability, complicating treatment. If these issues are addressed, Amtagvi possesses the ability to address the sizable potential market for solid tumors unlike other cell and gene therapy (CGT) agents so far. Amtagvi is expected to enjoy the majority share and first-to-market advantage, while other pipeline CGT agents remain in development.”