Full Press Release Details
Iovance's AMTAGVITM (lifileucel)
Receives U.S. FDA Accelerated Approval
for Advanced Melanoma
AMTAGVI is the first FDA-approved T cell therapy
for a solid tumor cancer and first treatment option for advanced melanoma after anti-PD-1 and targeted therapy
AMTAGVI deploys patient-specific immune cells
that recognize and fight cancer
SAN CARLOS, Calif., February 16, 2024 -- Iovance
Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing and delivering novel polyclonal tumor
infiltrating lymphocyte (TIL) cell therapies for patients with cancer, today announced that the U.S. Food and Drug Administration (FDA)
has approved AMTAGVITM (lifileucel) suspension for intravenous infusion. 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
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 AMTAGVITM 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.1
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 AMTAGVITM 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,2 (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 these 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 up,2 (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 AMTAGVITM 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, IovanceCaresTM, 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. For more information, physicians and patients may call 833-400-IOVA (4682) or visit www.iovancecares.com.
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.1
For more information, please visit: https://www.iovance.com/clinical-trials/.
1National Cancer Institute Surveillance, Epidemiology and
End Results (SEER) Program. 2023 Estimates. https://seer.cancer.gov accessed February 2024.
2Kaplan-Meier estimate of median potential follow-up for
duration of response.
*A single dose of AMTAGVI contains 7.5 109 to 72
Webcast and Conference Call
will host a conference call and live audio webcast to discuss the FDA approval of AMTAGVI today, details will be shared in a subsequent
About the C-144-01 Clinical Trial
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.
What is AMTAGVI (lifileucel)?
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.
Important Safety Information
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