Iovance Biotherapeutics’ Amtagvi Gains Fda Approval

US FDA approves Iovance Biotherapeutics Amtagvi for advanced melanoma
Iovance Biotherapeutics, Inc., a biotechnology company focused on innovating, developing and delivering novel polyclonal tumour infiltrating lymphocyte (TIL) cell therapies for patients with cancer, announced that the US Food and Drug Administration (FDA) has approved 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.

Mechanism

Amtagvi is the first and the only one-time, individualized T cell therapy to receive FDA approval for a solid tumour 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 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 in Patient Care

Amtagvi is manufactured using a proprietary process to collect and expand a patient’s unique T cells from a portion of their tumour. 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).

Words from Leader

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 tumour cancers, making our novel cell therapies available to more patients with melanoma and other types of cancers.

Melanoma Facts

Each year, approximately 8,000 people in the US 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.

Melanoma Foundation Statement

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.

Responses Form Trials

• 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 Tumours (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. 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: Warnings and Precautions

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.

Praises from Cancer Industry’s Prominent Figures

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 tumours.

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 tumours,” added Dr. Jae Park, Chief of Cellular Therapy Service at Memorial Sloan Kettering Cancer Center.

Future Plans & Precautions

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 tumours. Amtagvi must be administered in an ATC, and more than 30 ATCs are prepared to collect and ship tumour tissue from patients for Amtagvi manufacturing.

About Iovance

Iovance is dedicated to providing access to Amtagvi for patients with advanced melanoma. A comprehensive support programme, 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 tumour types, which represent 91% of the cancers in the US.

What is C-144-01?

C-144-01 is a global, multicenter Phase 2 study in which patients received treatment with lifileucel. The study enrolled patients with metastatic melanoma who were previously treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor. Efficacy was established on the basis of objective response rate (ORR), and duration of response (DOR) by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The pivotal Cohort 4 and supportive Cohort 2 of Study C-144-01 enrolled patients that met the same primary eligibility criteria, had the same assessments, and had received the same regimen and Amtagvi that was produced using the same manufacturing process, and product formulation. The detailed results of C-144-01 were published in the Journal for ImmunoTherapy of Cancer in 2022.

Amtagvi

Amtagvi is a prescription medicine used to treat adults with a type of skin cancer that cannot be removed surgically or has spread to other parts of the body called unresectable or metastatic melanoma.

Amtagvi is used when your melanoma has not responded or stopped responding to a PD-1 blocking drug either by itself or in a combination, and if your cancer is BRAF mutation positive, a BRAF inhibitor drug with or without a MEK inhibitor drug that has also stopped working.

The approval of Amtagvi is based on a study that measured response rate. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

Iovance Biotherapeutics aims to be the global leader in innovating, developing and delivering tumour infiltrating lymphocyte (TIL) cell therapies for patients with cancer.

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