Iovance Biotherapeutics has announced groundbreaking five-year results from its Phase 2 C-144-01 clinical trial evaluating Amtagvi (lifileucel) in patients with advanced melanoma. The data, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that the one-time cell therapy treatment achieved a five-year overall survival rate of 19.7% in patients who had previously failed anti-PD-1 and targeted therapy.
Unprecedented Long-Term Survival Data
The long-term data comes 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 overall survival of 13.9 months, with approximately one-fifth of patients surviving at the five-year mark. This represents the longest follow-up in a multicenter tumor infiltrating lymphocyte (TIL) therapy study.
The objective response rate was 31.4%, including complete responses in 5.9% of patients and partial responses in 25.5%. Among patients who responded to treatment, the median duration of response was 36.5 months, with 31.3% of responders completing the five-year assessment with ongoing responses.
"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," said Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance.
Safety Profile Consistent with Previous Reports
The safety profile remained consistent with known effects of nonmyeloablative lymphodepletion and interleukin-2 administration. Importantly, the incidence of adverse events decreased rapidly within the first two weeks after Amtagvi infusion, and there were no new or late-onset treatment-related adverse events reported.
Common side effects of the Amtagvi treatment included chills, fever, low white blood cell count, fatigue, low red blood cell count, fast or irregular heartbeat, rash, low blood pressure, and diarrhea.
First FDA-Approved Cell Therapy for Solid Tumors
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.
This approval marked a significant milestone as Amtagvi became the first one-time T cell therapy approved for a solid tumor cancer, as well as the first treatment option specifically for patients with advanced melanoma after anti-PD-1 and targeted therapy.
"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," noted Dr. Finckenstein.
How Amtagvi Works
Amtagvi represents a personalized approach to cancer treatment. The therapy is created from a patient's own immune cells that are extracted from their surgically removed tumor tissue. These tumor-infiltrating lymphocytes (TILs) are then multiplied in a laboratory setting until they number in the billions before being reinfused back into the patient.
The manufacturing process takes approximately 34 days from the time tumor tissue is received at the manufacturing center until Amtagvi is available to be shipped back to the healthcare provider. Prior to infusion, patients undergo lymphodepleting chemotherapy to prepare their body for the cell therapy.
Ongoing Research and Future Directions
Iovance is also conducting TILVANCE-301, a Phase 3 trial in frontline advanced melanoma to confirm clinical benefit. Additionally, the company is exploring the potential of TIL therapy in other solid tumors, including non-small cell lung cancer.
A Phase 2 multicenter study of the lifileucel regimen and pembrolizumab after frontline platinum-doublet chemotherapy and pembrolizumab in advanced non-small cell lung cancer is currently in progress, with details presented at ASCO.
Clinical Implications
The five-year data from the C-144-01 trial is particularly significant given the limited treatment options available for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapy. The durable responses observed with Amtagvi suggest that TIL therapy may offer a viable treatment strategy for patients with limited alternatives.
For patients with advanced melanoma who have exhausted standard treatment options, these results provide hope for a therapy that could potentially offer long-term disease control from a single treatment, representing a paradigm shift in the management of this challenging disease.
