On May 22, 2025 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported five-year results from the Phase 2 C-144-01 clinical trial evaluating the individualized T cell therapy Amtagvi (lifileucel) (Press release, Iovance Biotherapeutics, MAY 22, 2025, View Source [SID1234653308]).

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The C-144-01 trial investigated Amtagvi in patients with advanced melanoma previously treated with anti-PD-1 and targeted therapy, where applicable. The five-year results included meaningful overall survival (OS) results and durable responses following one-time treatment with Amtagvi. These results will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

The long-term data are from 153 patients combined from cohorts 2 and 4 of the C-144-01 trial. With a median follow-up of 57.8 months, patients achieved a median OS of 13.9 months, with 19.7% of patients surviving at the five-year mark. The objective response rate was 31.4%, including complete responses in 5.9% of patients and partial response in 25.5%. Among patients who responded to treatments, the median duration of response was 36.5 months. Nearly a third of responders (31.3%) completed the five-year assessment with ongoing responses.

Adverse events (AEs) were consistent with known safety profiles of nonmyeloablative lymphodepletion and interleukin-2 administration. The incidence of AEs decreased rapidly within the first two weeks after Amtagvi infusion, and there were no new or late-onset treatment-related AEs.

"As the first one-time cell therapy approved for a solid tumor cancer, Amtagvi offers a compelling and differentiated treatment option, potentially transforming care within the advanced melanoma community," said Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance. "These five-year data represent the longest follow-up in a multicenter TIL therapy study, reinforcing the deep and lasting responses, and favorable long-term safety with Amtagvi. In addition, we remain committed to realizing the potential of novel T cell therapies for difficult-to-treat solid tumor cancers representing 90 percent of all diagnosed cancers today."

Additional details will be presented at ASCO (Free ASCO Whitepaper):

Rapid Oral Presentation: Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study (Abstract 9515)
Session: Melanoma/Skin Cancers, Monday, June 2, 2025, 9:45 am – 11:15 am CDT
Trial-in-Progress Poster: Phase 2, multicenter study of the lifileucel regimen and pembrolizumab after frontline platinum-doublet chemotherapy and pembrolizumab in advanced non-small cell lung cancer (Abstract TPS8659)
Session: Lung Cancer—Non-Small Cell Metastatic, Saturday, May 31, 2025, 1:30 pm – 4:30 pm CDT
Iovance will host a panel discussion on the evening of Saturday, May 31, 2025 at 6:15 pm CDT (7:15 pm EDT) featuring key opinion leaders in melanoma. Please register here to listen to the live audio webcast or replay: View Source The live and archived webcast will be available in the Investors section of the company’s website at www.iovance.com.

In February 2024, the U.S. Food and Drug Administration granted accelerated approval to Amtagvi 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. The approval is based on overall response rate and duration of response from the C-144-01 clinical trial. With this approval, Amtagvi became the first one-time T cell therapy for a solid tumor cancer as well as the first treatment option for patients with advanced melanoma after anti-PD-1 and targeted therapy. Iovance is also conducting TILVANCE-301, a Phase 3 trial in frontline advanced melanoma to confirm clinical benefit.

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 lifileucel 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.

About 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.

Important Safety Information

What is the most important information that I should know about AMTAGVI?

You will likely be in a hospital prior to and after receiving AMTAGVI.

Before taking AMTAGVI, tell your healthcare provider about all of your medical conditions, including if you:

Have any lung, heart, liver or kidney problems
Have low blood pressure
Have a recent or active infection or other inflammatory conditions including cytomegalovirus (CMV) infection, hepatitis B or C or human immunodeficiency virus (HIV) infection
Are pregnant, think you may be pregnant, or plan to become pregnant
Are breastfeeding
Notice the symptoms of your cancer are getting worse
Have had a vaccination in the past 28 days or plan to have one in the next few months
Have been taking a blood thinner
Tell your doctor about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive AMTAGVI?

AMTAGVI is made from your surgically removed tumor. Tumor derived T cells are grown in a manufacturing center at the end of which they number in the billions of cells.
Your tumor tissue is sent to a manufacturing center to make AMTAGVI. It takes about 34 days from the time your tumor tissue is received at the manufacturing center until AMTAGVI is available to be shipped back to your healthcare provider, but the time may vary. Your AMTAGVI will be provided in 1-4 patient-specific infusion bag(s) containing 100 mL to 125 mL of viable (alive) cells per bag.
After your AMTAGVI arrives at your treating institution, your healthcare provider will give you lymphodepleting chemotherapy to prepare your body.
Approximately 30 to 60 minutes before you are given AMTAGVI, you may be given other medicines including:
Medicines for an allergic reaction (anti-histamines)
Medicines for fever (such as acetaminophen)
Your AMTAGVI will be provided in 1 to 4 infusion bag(s) containing 100 mL to 125 mL of viable cells per bag. When your body is ready for AMTAGVI infusion, your healthcare provider will give AMTAGVI to you by intravenous infusion. This usually takes less than 90 minutes.
After getting AMTAGVI

Beginning 3 to 24 hours after AMTAGVI is given, you may be given up to 6 doses of IL-2 (aldesleukin) every 8 to 12 hours via intravenous infusion. Your doctor may discontinue IL-2 (aldesleukin) infusion any time if you have severe side effects.

You will have to stay in the hospital until you have completed the IL-2 (aldesleukin) treatment and you have recovered from any serious side effects associated with the AMTAGVI treatment.

You should plan to stay within 2 hours of the location where you received your treatment for several weeks after getting AMTAGVI. Your healthcare provider will check to see if your treatment is working and help you with any side effects that occur.

What are the possible side effects of AMTAGVI?

The most common side effects of the AMTAGVI treatment include chills, fever, low white blood cell count (may increase risk of infections), fatigue, low red blood cell count (may cause you to feel tired or weak), fast or irregular heartbeat, rash, low blood pressure, and diarrhea.

These are not all the possible side effects of the AMTAGVI treatment. Talk with your healthcare provider for more information about AMTAGVI. You can ask your healthcare provider for information about AMTAGVI that is written for healthcare professionals.

You may report side effects to Iovance at 1-833-400-4682, or to the FDA, at 1-800-FDA-1088 or at www.fda.gov/medwatch.

Please see Full Prescribing Information and Patient Information, including Boxed Warning, for additional Important Safety Information.