Results from the Phase II C-144-01 trial show that Iovance Biotherapeutics’ Amtagvi (lifileucel) demonstrated deep and durable responses in patients with advanced melanoma previously treated with anti-PD-1 and targeted therapies. Full five-year results were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The Journal of Clinical Oncology.¹

Can a One-Time T-Cell Therapy Offer Lasting Benefit in Advanced Melanoma?

“Amtagvi has demonstrated long-term benefit and meaningful overall survival in a difficult-to-treat melanoma patient population resistant to immune checkpoint inhibitor therapy,” said Theresa Medina, MD, medical oncologist, University of Colorado Cancer Center on the Anschutz Medical Campus, in a press release. “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.”

Trial Design and Patient Population

• The global, multicenter C-144-01 trial evaluated Amtagvi in 153 patients with metastatic melanoma who were previously treated with at least one systemic therapy.
• Additionally, this included patients who were treated with a BRAF inhibitor or BRAF inhibitor with MEK inhibitor if BRAF V600 mutation-positive.
• Cohort 2 included 66 patients while cohort 4 included 87 patients.
• The primary endpoint of the trial was objective response rate (ORR) as assessed by an Independent Review Committee using RECIST v1.1 criteria.

Key Efficacy Outcomes

• Results show that a single fusion of Amtagvi demonstrated a 31.4% ORR.
• Additionally, results demonstrated a median duration of response of 36.5 months
• Median overall survival was 13.9 months.
• Notably, 31.3% of responders completed the five-year assessment with ongoing responses.

Safety and Tolerability

• The safety profile of the treatment remained consistent with that of nonmyeloablative lymphodepletion and interleukin-2 administration.
• The incidence of adverse events (AEs) decreased significantly within the first two weeks of treatment, with no new or late-onset treatment-related AEs.1
• Deaths due to AEs, which were unrelated to treatment, included septic shock, failure to thrive, cerebral hemorrhage, multiple organ dysfunction syndrome, pulmonary embolism, and intracranial hemorrhage.
• Deaths due to treatment-related AEs included pneumonia, arrhythmia related to cyclophosphamide, acute respiratory failure, intra-abdominal hemorrhage related to all components of the treatment, and bone marrow failure related to all components of the treatment.²

Melanoma Impact and Regulatory Context

According to the American Cancer Society, melanoma is the most common form of cancer in the United States, accounting for a majority of skin cancer–related deaths. However, the death rate from melanoma declined significantly from 2013 to 2022.³

FDA Approval and Future Directions

“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, MD, chief medical officer, Iovance, in a press release. “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.”⁴

The FDA first granted accelerated approval to Amtagvi in February 2024 for the treatment of 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 regulatory action marked the first one-time T-cell therapy approved for a solid tumor cancer as well as the first treatment option for patients with advanced melanoma following anti-PD-1 and targeted therapy.⁴

References

1. The Journal of Clinical Oncology Publishes Five-year Analysis of Amtagvi® (lifileucel) in Patients with Advanced Melanoma. Iovance. June 2, 2025. Accessed June 6, 2025. https://ir.iovance.com/news-releases/news-release-details/journal-clinical-oncology-publishes-five-year-analysis-amtagvir

2. Author's Accepted Manuscript. ASCO. Accessed June 6, 2025. https://ascopubs.org/doi/pdfdirect/10.1200/JCO-25-00765

3. Iovance Announces Five-year Results of Amtagvi® (lifileucel) in Patients with Advanced Melanoma at ASCO Annual Meeting. Iovance. May 22, 2025. Accessed June 6, 2025. https://ir.iovance.com/news-releases/news-release-details/iovance-announces-five-year-results-amtagvir-lifileucel-patients

4. Key Statistics for Melanoma Skin Cancer. American Cancer Society. AccessedJune 6, 2025. https://www.cancer.org/cancer/types/melanoma-skin-cancer/about/key-statistics.html