One-time TIL therapy shows durable responses in advanced lung cancer

A one-time tumor infiltrating lymphocyte (TIL) therapy showed durable responses in previously treated nonsquamous non-small cell lung cancer (NSCLC), according to new interim results from a phase 2 study. Iovance Biotherapeutics reported a 25.6% objective response rate and a median duration of response that has not yet been reached after more than two years of follow-up. The findings, announced Nov. 3 by the San Carlos, California–based company, suggest a potential option for patients who have few effective treatments after their cancer has progressed despite chemoimmunotherapy.

Lung cancer remains the leading cause of cancer death worldwide and accounts for an estimated 226,000 new cases and 125,000 deaths annually in the United States. Approximately 85% of cases are NSCLC, with nonsquamous tumors making up the majority of the NSCLC cases.

“It is exciting to see such an impressive response rate and durability observed in previously treated patients with NSCLC, because today there are only very limited treatment options, noneof which demonstrate this quality of response and durability,” said Martin Wermke, M.D., of the University of Dresden in Germany, in the news release. Standard-of-care docetaxel in a similar patients has historically produced an objective response rate of 12.8%, a median duration of response of 5.6 months and no complete responses.

The IOV-LUN-202 study is an ongoing multicenter, prospective, open-label phase 2 clinical trial evaluating lifileucel in patients with metastatic or unresectable nonsquamous NSCLC without EGFR, ROS1 or ALK gene mutations. All enrolled patients had previously received an immune checkpoint inhibitor and chemotherapy. Patients received a high-dose lymphodepleting regimen followed by infusion of their own expanded TIL product and supportive interleukin-2.

Among the first 39 patients evaluated by central review using standard criteria, 10 achieved an objective response, including two complete responses, seven partial responses and one unconfirmed partial response awaiting verification. Median follow-up was 25.4 months, and the median duration of response had not been reached.

If confirmed in the full study population, the findings suggest that a one-time individualized therapy may offer a new option for patients whose cancer has progressed after standard treatments.

Background on TIL

TIL therapy builds on work pioneered more than three decades ago by the National Cancer Institute researchers. Unlike chimeric antigen receptor therapy (CAR-T), which genetically engineers circulating T cells to target cancer, TIL therapy uses immune cells harvested directly from a patient’s tumor. The collected TILs are expanded into billions of cells in a laboratory, typically with interleukin-2, and reinfused after a short course of high-dose lymphodepleting chemotherapy. Amtagvi (lifileucel) first entered clinical use when the FDA granted accelerated approval in February 2024 for adults with advanced melanoma whose disease had progressed despite prior immunotherapy or targeted therapy. The decision marked the first approval of a TIL-based therapy and the first cellular therapy authorized for any solid tumor. A single treatment is priced at $515,000, similar to the cost of CAR-T therapies.

In the pivotal melanoma study that supported FDA approval, nearly one-third of participants experienced a tumor response, including several complete responses. About 40% of responders remained progression-free one year after receiving a single infusion. Most side effects were attributed to lymphodepleting chemotherapy and post-infusion IL-2, and investigators noted that TIL therapy did not produce the severe cytokine release syndrome or neurologic toxicity associated with CAR T-cell products.

Investigators are evaluating lifileucel in multiple settings beyond melanoma, including a combination regimen with Keytruda (pembrolizumab) and studies in ovarian, head and neck, and lung cancers.

The new NSCLC findings add to that clinical development program and reflect growing interest in personalized TIL therapy for solid tumors.