Patients with advanced melanoma achieved deep and durable responses after receiving the tumor-infiltrating lymphocyte (TIL) therapy lifileucel alongside the immune checkpoint inhibitor pembrolizumab as a first-line treatment, according to results from a new clinical trial. Approximately two-thirds (62.5%) of patients saw their tumors shrink significantly, with many experiencing substantial and long-lasting responses to the combined treatment.
These findings from the IOV-COM-202 clinical trial, an international, multicenter phase II trial conducted at The Royal Marsden NHS Foundation Trust, were presented at the European Society for Medical Oncology Congress 2026 by Andrew Furness, MD, PhD, Consultant Medical Oncologist and Solid Tumor Cellular Therapy Lead at The Royal Marsden NHS Foundation Trust and Leader of the Cellular Therapy and Translational Immunology Group at The Institute of Cancer Research, London (Abstract 2072O).
The findings suggest that introducing lifileucel earlier in the treatment pathway may improve outcomes for patients. In 2024, lifileucel became the first cellular therapy approved by the U.S. Food and Drug Administration for solid tumors after the C-144-01 clinical trial demonstrated a response rate of 31.4% in patients whose cancer had progressed following previous treatments.
The IOV-COM-202 study aimed to understand whether the therapy could deliver greater benefit when used earlier in the course of the disease.
Key Findings
The trial selected 27 patients with advanced melanoma and treated them with a combination of pembrolizumab and lifileucel. Patients first received chemotherapy before receiving the cell infusion and a short course of interleukin-2. Of the 27 patients treated, 24 were included in the trial’s main analysis.
After a median follow-up period of 26.9 months, researchers found that 15 of the 24 patients (62.5%) experienced significant tumor shrinkage, with approximately one-third (29.2%) of patients seeing their tumors disappear completely on scans. The median duration of response had not yet been reached more than 2 years after the trial began.
Among the 15 patients whose cancer responded to treatment, 13 maintained their response for at least 12 months, whereas 10 remained in complete or partial response at their most recent assessment.
Median progression-free survival was 19.8 months. Median overall survival had not yet been reached after 50.9 months of follow-up. Patients experienced no additional side effects beyond those associated with the individual treatments.
Researchers are now evaluating this approach in TILVANCE-301 (ClinicalTrials.gov identifier NCT05727904), an international phase III trial comparing lifileucel plus pembrolizumab with pembrolizumab alone in patients with advanced melanoma, for which Dr. Furness is the U.K. National Chief Investigator.
He commented, “Immune checkpoint inhibitors like pembrolizumab have transformed outcomes for patients with advanced melanoma, with around half of patients achieving long-term cancer control. However, for those that do not derive long-term benefit, novel therapeutic options are urgently required. Our findings suggest that adding TIL therapy to first-line pembrolizumab can produce deep and durable responses. Larger studies will now help us understand which patients are most likely to benefit from this combination and how it can best be used alongside existing immunotherapies.”
About the Study Drugs
Lifileucel is a TIL therapy, which harnesses the power of a patient’s immune system by extracting immune cells from a patient’s tumor, multiplying them in a laboratory, and returning them to the bloodstream, allowing them to more effectively recognize and attack cancer cells. Pembrolizumab, an immune checkpoint inhibitor, is a proven first-line treatment for many patients with advanced melanoma. However, a significant fraction of patients do not experience long-lasting benefit. Lifileucel has been shown to offer a second chance at long-lasting cancer control when standard immunotherapies, including pembrolizumab, are no longer effective. The IOV-COM-202 trial sought to determine the potential benefit of combining both therapies as a first-line treatment.
DISCLOSURE: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
