Key Takeaways
- Amtagvi shows lasting benefit in advanced melanoma: A single infusion of the tumor infiltrating lymphocyte therapy Amtagvi (lifileucel) achieved a 31.4% objective response rate with durable responses lasting a median of 36.5 months.
- Five-year follow-up underscores safety and durability: Long-term data showed no new or late-onset treatment-related adverse events, with over 31% of responders maintaining benefit at five years.
- First approved one-time cell therapy for a solid tumor: Amtagvi received accelerated FDA approval in 2024, becoming the first one-time T-cell therapy available for patients with unresectable or metastatic melanoma after anti-PD-1 and targeted therapies.
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
