FDA approves Amtagavi for treatment of Advanced melanoma

The US Food and Drug Administration has approved first cellular therapy Amtagavi for treatment of Advanced melanoma. It is one-time cell therapy for patients who have progressed after initial standard-of-care therapies.

Approval of Amtagvi has been granted to Iovance Biotherapeutics.

AMTAGVI is a tumor-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, 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. TIL cells recognize distinctive tumor 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.* Authorized 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 accelerated approval of AMTAGVI™ is the first step in realizing Iovance’s ambition to usher in the next generation of cell therapy by bringing this breakthrough to patients with advanced solid tumors,” said Frederick Vogt, Ph.D., J.D., Interim Chief Executive Officer and President of Iovance. “Given the significant unmet needs in the advanced melanoma community, we are proud to offer a personalized, one-time therapeutic option for these patients. We are continuing our development efforts to address additional unmet medical needs in patients with solid tumor cancers, making our novel cell therapies available to more patients with melanoma and other types of cancers.”

Each year, approximately 8,000 people in the U.S. die from melanoma. Until now, there have been no FDA-approved treatment options for patients with advanced melanoma whose disease progressed following initial treatment with an immune checkpoint inhibitor and, if appropriate, targeted therapy.

“The approval of AMTAGVI™ offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” said Samantha R. Guild, J.D., President, AIM at Melanoma Foundation. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

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-up (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).

AMTAGVI is for autologous use only. AMTAGVI has a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Warnings and precautions include treatment-related mortality, prolonged severe cytopenia, internal organ hemorrhage, severe infection, cardiac disorder, respiratory failure, acute renal failure, and hypersensitivity reactions. Please see Important Safety Information and Prescribing Information below.

“This landmark FDA approval reflects significant advancements in TIL 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,” said Steven Rosenberg, M.D., Ph.D., Chief, Surgery Branch, National Cancer Institute, and a TIL and immunotherapy pioneer. “This approval is transformative for the entire research field and supports continued investigation of TIL cell therapy across additional types of solid tumors.”

“One-time treatment with AMTAGVI™ offered clinically meaningful and deep, durable responses in the Phase 2 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,” said Dr. Alexander N. Shoushtari, Melanoma Oncologist & Cellular Therapist at Memorial Sloan Kettering Cancer Center. “This welcome news represents an important step forward in harnessing cell therapy to treat solid tumors,” added Dr. Jae Park, Chief of Cellular Therapy Service at Memorial Sloan Kettering Cancer Center.

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. Additional expansion at iCTC is underway, which will 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.

Iovance is dedicated to providing access to AMTAGVI for patients with advanced melanoma. A comprehensive support program, IovanceCares™, is now available for patients and ATCs throughout the treatment journey. IovanceCares will also offer copay support, financial assistance, and travel and lodging assistance for eligible patients during AMTAGVI therapy. 

Iovance is investigating AMTAGVI in frontline advanced melanoma in the Phase 3 confirmatory trial, TILVANCE-301, as well as additional solid tumor types, which represent 91% of the cancers in the U.S.