Five-year follow-up data from a pivotal clinical trial demonstrate that a single infusion of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, provides durable survival benefits for patients with advanced melanoma who have exhausted standard treatment options. The results from the C-144-01 Phase 2 study were presented at the 2025 American Society for Clinical Oncology (ASCO) annual meeting.
Trial Design and Patient Population
The global, multicentre Phase 2 study enrolled 153 patients across Europe and the United States, with The Royal Marsden NHS Foundation Trust serving as the lead UK centre. All participants had metastatic melanoma refractory to standard approaches, including targeted therapies and checkpoint inhibitors.
The therapy involves isolating T cells from a cancer site, expanding and activating them in laboratory conditions, then reinfusing the enhanced cells back into the patient. These modified cells demonstrate improved ability to recognize and attack cancer cells.
Efficacy Outcomes
The trial achieved significant clinical outcomes in this heavily pretreated patient population. Tumor shrinkage occurred in 79.3% of patients overall, with 5.9% achieving complete response, defined as no evidence of cancer. Among patients who responded to treatment, 31.4% maintained their response at the five-year follow-up.
Some patients experienced deepening responses over time, progressing from partial to complete response even a year after treatment. The median overall survival reached 13.9 months, with 19.7% of patients remaining alive at five years.
Safety Profile
No new or delayed side effects related to the therapy were reported during the five-year follow-up period, supporting the long-term safety profile of the treatment approach.
Patient Experience
Zoe Phillips, a 46-year-old patient from Dorset diagnosed with stage 4 metastatic melanoma in 2023, participated in a first-line TIL therapy trial at The Royal Marsden. "Six weeks after my first TIL therapy treatment my scans showed that the tumours had completely disappeared," Phillips said. "Before coming to The Royal Marsden I was told that I would probably die, so hearing that my treatment had been successful was amazing."
Phillips continues to receive pembrolizumab immunotherapy treatment and currently shows no evidence of cancer.
Clinical Significance
Dr. Andrew Furness, Consultant Medical Oncologist who led the trial at The Royal Marsden NHS Foundation Trust, emphasized the therapy's potential impact. "While current forms of immunotherapy have revolutionised the treatment of cancer in recent years, overall these benefit a minority rather than majority of treated patients. Results from this trial have shown that TIL therapy may change the outlook for people with advanced melanoma."
Professor James Larkin, Consultant Medical Oncologist at The Royal Marsden and Professor at The Institute of Cancer Research, London, described the findings as transformative. "The study demonstrates that for patients with few options left, a single infusion of lifileucel can provide a deep and lasting response and even complete remission in some cases. This marks a major advance in how we think about treating solid tumours."
Regulatory Status and Future Development
Lifileucel received FDA approval for advanced melanoma treatment in 2024, becoming the first cellular therapy approved for solid tumors. Regulatory review is currently underway in Europe and the UK.
Building on these results, lifileucel is being evaluated in combination with pembrolizumab as first-line treatment for newly diagnosed patients with advanced melanoma in the TILVANCE-301 Phase 3 trial.
The research team continues investigating TIL therapy applications across multiple cancer types, including advanced lung, liver, ovary, skin and testicular cancers, as well as soft tissue sarcoma.
