29.2% complete response rate with lifileucel plus pembrolizumab

Among 24 patients with advanced melanoma in the main analysis of IOV-COM-202, lifileucel plus pembrolizumab produced significant tumor shrinkage in 62.5% and complete disappearance of tumors on scans in 29.2%. These results came from an international, multicenter Phase II trial conducted at The Royal Marsden NHS Foundation Trust and presented at the 2026 European Society for Medical Oncology Congress.

Investigators tested the combination as first-line treatment for advanced melanoma. The report did not describe randomization or a concurrent control arm, so the response rates establish neither superiority to pembrolizumab alone nor the contribution of each component.

What did the trial test?

The study treated 27 patients and included 24 in the main analysis; it did not state why three treated patients were excluded. Every patient first received chemotherapy to prepare the body, followed by a lifileucel cell infusion and a short course of interleukin-2, a drug that boosts immune-cell activity and helps the infused cells grow and attack cancer.

Lifileucel is a tumor-infiltrating lymphocyte (TIL) therapy: clinicians extract immune cells from a patient’s tumor, multiply them in a laboratory, and return them to the bloodstream so they can recognize and attack cancer cells more effectively. Pembrolizumab is an immune checkpoint inhibitor that blocks proteins restraining immune activity, allowing T cells to detect and attack cancer cells.

Pembrolizumab is a proven first-line treatment for many patients with advanced melanoma, although a substantial proportion does not receive lasting benefit. The trial therefore asked whether adding lifileucel at the outset could deepen and extend the response achieved with standard checkpoint blockade.

How durable were the responses?

After a median follow-up of 26.9 months, 15 of 24 patients had significant tumor shrinkage and 29.2% achieved complete response. Median duration of response had not been reached more than two years after the trial began, meaning that response duration could not be estimated at this analysis.

• Among the 15 patients whose cancer responded, 13 maintained a response for at least 12 months.
• Ten remained in complete or partial response at their most recent assessment.
• Median progression-free survival, the interval before cancer returned or progressed, was 19.8 months.
• Median overall survival, the period during which patients remained alive, had not been reached after 50.9 months of follow-up.

The report gives 26.9 months as median follow-up for the response analysis and 50.9 months for the overall-survival statement, without explaining the differing intervals. The response figures are encouraging, but the analysis remains too small to characterize benefit across melanoma subgroups.

What does the safety finding establish?

Investigators reported no additional side effects beyond those associated with the individual treatments. That finding is favorable, but the main analysis included only 24 patients and the report provided no detailed toxicity breakdown. The small group also cannot exclude uncommon or delayed harms.

Does earlier treatment establish a new standard?

The strategy tests whether lifileucel works better when introduced earlier, but that benefit remains unproven. In 2024, lifileucel became the first cellular therapy approved by the US Food and Drug Administration (FDA) for solid tumors after C-144-01 demonstrated a 31.4% response rate in patients whose cancer had progressed following previous treatment.

That earlier response rate came from a pretreated, later-line population, whereas IOV-COM-202 used first-line treatment; the figures therefore do not constitute a head-to-head comparison. Lifileucel had already shown durable cancer control as a later-line option after standard immunotherapies, including pembrolizumab, stopped working. Moving it forward could improve outcomes, but a comparative trial is required to test that proposition.

Dr Andrew Furness presented the results at the 2026 ESMO Congress. He is consultant medical oncologist and solid tumor cellular therapy lead at The Royal Marsden, leader of the Cellular Therapy and Translational Immunology Group at the Institute of Cancer Research (ICR), London, and Honorary Faculty at ICR.

Furness said: “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,” he said.

What did the response mean for patients?

Paul Jenner, 59, a retired former ballet dancer and owner of a landscape construction company in London, joined the trial after a 2024 melanoma diagnosis. Referral to The Royal Marsden followed tests showing spread beyond the original site to nearby lymph nodes; he received lifileucel and pembrolizumab in August 2024 and remains in remission.

Before treatment, his cancer had spread to his lung, with a growth on his back and two other areas under observation. Jenner said: “These all disappeared after the TIL therapy and pembrolizumab.”

He described the use of his own cells to heal him as amazing, expressed gratitude for the chance to receive TIL therapy, and praised the ward and research staff. He also said he did not know where he would be without the treatment.

What will the Phase III trial determine?\n

Researchers are now evaluating the approach in TILVANCE-301, an international Phase III trial comparing lifileucel plus pembrolizumab with pembrolizumab alone in advanced melanoma. Furness serves as UK National Chief Investigator, and the comparison directly addresses the uncertainty left by the Phase II study without a described concurrent control.

Iovance Biotherapeutics funded IOV-COM-202. Solid-tumor cellular-therapy research at The Royal Marsden also received support from supporters of The Royal Marsden Cancer Charity, charity partner Nationwide, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and ICR; Furness’s role is part-funded by The Royal Marsden Cancer Charity.

Phase III results will test whether first-line lifileucel adds durable benefit to pembrolizumab alone and whether that benefit is concentrated in a defined subgroup of patients.