Novel immunotherapy approved for melanoma

Amtagvi (lifileucel) is the first tumour-derived autologous T cell immunotherapy therapy to be approved by the US Food and Drug Administration (FDA) for certain adults with unresectable or metastatic melanoma.

It is also the first non-CAR-T adoptive cell therapy to reach the market. Based on the FDA’s approval, lifileucel is indicated in those who have previously has been treated with other therapies (a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor).

Dr Peter Marks, PhD, Director of the FDA’s Center for Biologics Evaluation and Research (CBER) stated that Amtagvi is a novel T cell immunotherapy for patients with limited treatment options.

Importance of the FDA’s approval

“This landmark FDA approval reflects significant advancements in tumour infiltrating lymphocytes (TIL) therapy cell therapy since we initially showed that TIL cells isolated from patients with metastatic melanoma could be expanded in the lab and returned to the patient to mediate cancer regression,” shared Dr Steven Rosenberg, PhD, Chief, Surgery Branch, National Cancer Institute, and a TIL and immunotherapy pioneer.

According to Iovance Biotherapeutics, when cancer is detected, the immune system creates TIL cells to find and destroy cancer. By identifying distinctive tumour markers on the cell surface, if a cancer continues to develop, the body’s natural TIL cells cannot continue to function.

“So far, we haven’t seen great success from CAR-T or other cell therapies in treating patients with solid tumours. However, by the very nature of TILs, we have years of data demonstrating them to be more successful for these cancer types,” Dr Jason Bock, CEO of the Cell Therapy Manufacturing Center (CTMC) in the US commented.

“Given the significant unmet needs in the advanced melanoma community, we are proud to offer a personalised, one-time therapeutic option for these patients,” remarked Frederick Vogt, PhD, JD, Interim Chief Executive Officer and President of Iovance Biotherapeutics.

“This welcome news represents an important step forward in harnessing cell therapy to treat solid tumours,” explained Dr Jae Park, Chief of Cellular Therapy Service at Memorial Sloan Kettering Cancer Center.

Clinical efficacy of the immunotherapy Amtagvi

“One-time treatment with AMTAGVI™ offered clinically meaningful and deep, durable responses in the Phase II clinical trial, and I am excited by its potential as a much-needed new treatment option for the many advanced melanoma patients who progress on the current standard of care,” noted Dr Alexander Shoushtari, Melanoma Oncologist & Cellular Therapist at Memorial Sloan Kettering Cancer Center, US.

In the clinical study, the safety and effectiveness of Amtagvi was evaluated in adults with unresectable or metastatic melanoma given at least one systemic therapy, including a PD-1 blocking antibody, and if positive for the BRAF V600 mutation, a BRAF inhibitor or BRAF inhibitor with an MEK inhibitor.

 FDA highlighted that among the 73 patients treated with Amtagvi at the recommended dose:

• Objective response rate was 31.5 percent, including three (4.1 percent) patients with a complete response and 20 (27.4 percent) patients with a partial response
• In patients responsive to lifileucel, 56.5 percent, 47.8 percent and 43.5 percent continued to maintain responses without tumour progression or death at six, nine and 12 months, respectively.

Manufacturing the novel cellular therapy

According to Iovance Biotherapeutics, AMTAGVI will be manufactured at its site in Philadelphia, US, which is “the first FDA-approved, centralised, and scalable manufacturing facility dedicated to producing TIL cell therapies for patients with solid tumours.”

The FDA granted the approval of Amtagvi to Iovance Biotherapeutics.