Five-Year Analysis of Amtagvi® (lifileucel) in Advanced Melanoma Patients Published in The Journal of Clinical Oncology

One-time Amtagvi Treatment Continues to Show Deep, Durable Responses and Meaningful Survival

One Third of Responses Remain Ongoing without Subsequent Treatment after Five Years

Simultaneous Presentation at ASCO 2025

SAN CARLOS, Calif., June 02, 2025 – Iovance Biotherapeutics (NASDAQ: IOVA), a commercial biotechnology firm at the forefront of cancer treatment innovation, today unveiled compelling five-year follow-up data for its groundbreaking T cell therapy, Amtagvi® (lifileucel). The findings from the Phase 2 C-144-01 clinical trial, published in the *Journal of Clinical Oncology*, are being simultaneously presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, marking a significant milestone in the fight against advanced melanoma.

This extended analysis of the C-144-01 trial offers an unprecedented look at the long-term efficacy and durability of Amtagvi in a patient population with advanced melanoma, previously treated with anti-PD-1 therapies and targeted therapies where applicable. The study encompassed 153 patients from cohorts 2 and 4 of the trial.

The one-time Amtagvi treatment demonstrated sustained benefits in heavily pretreated patients, including deep and lasting responses, substantial overall survival without requiring further treatment, and no new or late-onset adverse events, with a median follow-up of 57.8 months. The objective response rate stood at 31.4%, with a median time to response of 1.4 months and a median duration of response of 36.5 months. Impressively, almost one-third of responders (31.3%) continued to experience ongoing responses at the five-year mark. The median overall survival (mOS) was 13.9 months, translating to a five-year survival rate of 19.7%. The survival outcomes were consistent among responders regardless of the timing of their response to Amtagvi.

The observed safety profile mirrored that typically seen with nonmyeloablative lymphodepletion and interleukin-2 administration. Adverse events decreased rapidly within the initial two weeks following Amtagvi infusion, with no new or delayed treatment-related adverse events reported.

Dr. Theresa Medina, a medical oncologist at the University of Colorado Cancer Center on the Anschutz Medical Campus, commented, “Amtagvi has demonstrated long-term benefit and meaningful overall survival in a difficult-to-treat advanced melanoma patient population that has demonstrated resistance to immune checkpoint inhibitor therapy. Five years following one-time Amtagvi treatment, responses persisted or deepened during an extended treatment-free interval for some patients. Amtagvi offers a new standard of care for the advanced melanoma community and sets a new bar for one-time cell therapies with curative intent in solid tumors.”

In February 2024, the U.S. Food and Drug Administration granted accelerated approval to Amtagvi for adult patients with unresectable or metastatic melanoma who had previously undergone treatment with a PD-1 blocking antibody and, if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor. The approval was based on the overall response rate and duration of response data from the C-144-01 clinical trial. This approval made Amtagvi the first one-time T cell therapy approved for a solid tumor cancer and the first approved treatment option for advanced melanoma patients following anti-PD-1 and targeted therapies. Iovance is also conducting the Phase 3 trial, TILVANCE-301, which will confirm the benefits of Amtagvi in frontline advanced melanoma.

About the C-144-01 Clinical Trial

C-144-01, a global, multicenter Phase 2 study, evaluated the use of lifileucel in patients with metastatic melanoma previously treated with a minimum of one systemic therapy, including a PD-1 blocking antibody and, for patients with BRAF V600 mutations, a BRAF inhibitor or a BRAF inhibitor combined with a MEK inhibitor. Efficacy was assessed based on the objective response rate (ORR) and duration of response (DOR) as determined by an Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients enrolled in the pivotal Cohort 4 and supportive Cohort 2 of the C-144-01 study fulfilled the same primary eligibility criteria, underwent identical assessments, and received the same Amtagvi regimen manufactured using the identical process and product formulation. The final five-year analysis of C-144-01 was published in the *Journal of Clinical Oncology* in 2025.

About Amtagvi®

AMTAGVI is an FDA-approved prescription medicine that treats adults with unresectable or metastatic melanoma.

It is used when a patient’s melanoma has not responded to, or has stopped responding to, a PD-1 blocking drug, either alone or in combination, along with a BRAF inhibitor drug with or without a MEK inhibitor drug (if the cancer is BRAF mutation positive).

The approval of AMTAGVI was based on response rates. Future approvals may depend on the results of ongoing studies to confirm Amtagvi’s benefits.

Important Safety Information

What are the most important things to know about AMTAGVI?

It is likely you will be in a hospital both before and after receiving AMTAGVI.

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

• Have any problems with your lungs, heart, liver, or kidneys.
• 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 might 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.
• Are taking blood thinners.

Inform 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 created using your surgically removed tumor. Tumor-derived T cells are grown in a manufacturing center, eventually multiplying into billions of cells.
• Your tumor tissue is sent to a manufacturing center to make AMTAGVI. The process from receiving your tumor tissue at the center to shipping AMTAGVI back to your healthcare provider usually takes about 34 days, but it can vary. Your AMTAGVI will be provided in one to four patient-specific infusion bags containing 100 mL to 125 mL of viable (living) cells per bag.
• Your doctor will give you lymphodepleting chemotherapy to prepare your body after your AMTAGVI arrives.
• Around 30 to 60 minutes before Amtagvi is administered, you’ll also be given other medicines such as:
  • Medicines to treat allergic reactions (anti-histamines).
  • Medicines for fever (such as acetaminophen).
• AMTAGVI will be administered via intravenous infusion; this typically takes under 90 minutes.

After getting AMTAGVI

Beginning 3 to 24 hours later, 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) if severe side effects occur.

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

Plan to stay within a two-hour radius of the treatment center for several weeks after receiving AMTAGVI. Your healthcare provider will assess the effectiveness of the treatment and manage any side effects that arise.

What are the possible side effects of AMTAGVI?

The most common side effects include chills, fever, low white blood cell count (potentially increasing risk of infections), fatigue, low red blood cell count (which may cause tiredness or weakness), rapid or irregular heartbeat, rash, low blood pressure, and diarrhea.

This isn’t an exhaustive list of AMTAGVI’s possible side effects. Consult with your healthcare provider for more information. You can also ask your healthcare provider for information about AMTAGVI written for healthcare professionals.

To report side effects, contact Iovance or the FDA.

See the Full Prescribing Information and Patient Information, including Boxed Warning, for additional Important Safety Information.

About Iovance Biotherapeutics, Inc.
Iovance Biotherapeutics is establishing itself as a leader in the development and delivery of tumor infiltrating lymphocyte (TIL) therapies for cancer patients. We are at the forefront of leveraging the immune system’s power to target and destroy diverse cancer cells. The Iovance TIL platform has shown promising results across an array of solid tumors. Amtagvi, from Iovance, is the first FDA-approved T cell therapy for solid tumors. We are committed to innovation in cell therapy, including gene-edited cell therapy, with the goal of extending and improving the lives of cancer patients. For more information, please visit http://www.iovance.com/.

Amtagvi^® and its accompanying design marks, Proleukin^®, Iovance, and IovanceCares™ are trademarks and registered trademarks of Iovance Biotherapeutics, Inc. or its subsidiaries. All other trademarks and registered trademarks are the property of their respective owners.

Forward-Looking Statements
Certain statements in this press release are “forward-looking statements”. They reflect Iovance Biotherapeutics, Inc.’s current views and expectations about future events and are subject to various risks, uncertainties, and assumptions. Please see the provided regulatory filings for comprehensive information about these potential risks.