Lifileucel Displays Antitumor Activity in Advanced Nonsquamous NSCLC

Lifileucel (Amtagvi) tumor-infiltrating lymphocyte (TIL) cell therapy generated responses with an expected safety profile in patients with previously treated, advanced nonsquamous non–small cell lung cancer (NSCLC) without certain actionable genetic mutations, according to data from an interim analysis of the phase 2 IOV-LUN-202 trial (NCT04614103).¹

In the trial, at a median follow-up of 25.4 months, one-time treatment with lifileucel monotherapy elicited an overall response rate (ORR) of 25.6% per RECIST 1.1 criteria (n = 10/39), including 2 complete responses (CRs), 7 partial responses (PRs), and 1 unconfirmed PR that was pending confirmatory assessment. Additionally, the disease control rate (DCR) was 71.8%, and the median duration of response (DOR) was not reached.

“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, none of which demonstrate this quality of response and durability,” Martin Wermke, MD, professor for experimental cancer therapy and director at the National Center for Tumor Diseases Dresden in Germany, stated in a news release. “One-time treatment with lifileucel monotherapy has the potential to benefit many patients with advanced NSCLC following initial treatment with an immune checkpoint inhibitor [ICI].”

The safety profile of lifileucel was deemed consistent with that of the underlying disease, non-myeloablative lymphodepletion, and interleukin-2 (IL-2), according to the news release. Additionally, an updated regimen of reduced non-myeloablative lymphodepletion that was introduced during the course of the trial has shown improvements in the overall safety profile of the treatment. Patients who received the updated regimen experienced a reduction in median hospitalization days following IL-2. These patients also had a lower incidence and shorter time to resolution of cytopenias vs those who received the initial regimen.

“Lifileucel has demonstrated a potentially best-in-class clinical profile in previously treated advanced nonsquamous NSCLC,” Friedrich Graf Finckenstein, MD, chief medical officer of Iovance—the developer of lifileucel—added in the news release. “The DOR is unprecedented and is combined with an impressive response rate in a one-time monotherapy for a difficult-to-treat patient population. We will pursue regulatory approvals for lifileucel monotherapy to effectively address the tens of thousands of patients with previously treated nonsquamous advanced NSCLC.”

What is the design of IOV-LUN-202?

This registrational, global trial is evaluating lifileucel monotherapy in patients with advanced (metastatic or unresectable) NSCLC that does not harbor EGFR, ROS1, or ALK actionable genetic mutations.^1,2 Patients must have previously received an ICI and chemotherapy. Patients also need to have at least 1 measurable lesion for TIL production and at least 1 remaining measurable lesion per RECIST 1.1 criteria, adequate organ function, a left ventricular ejection fraction over 45%, adequate pulmonary function, and an ECOG performance status of 0 or 1.²

Tumor samples are resected from each patient and cultured ex vivo to expand the TIL population. The patients then receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by lifileucel autologous TIL infusion, then IL-2.

The primary end point is ORR. Secondary end points include CR rate, DOR, DCR, progression-free survival, overall survival, adverse effects, and the feasibility of generating lifileucel using tumor tissue obtained via image-guided core biopsy.

Enrollment to this trial is planned to be completed in the second half of 2026.¹

Additional data from the IOV-LUN-202 trial are planned to be presented at a future medical meeting in 2026. IOV-LUN-202 is expected to support the submission of a supplemental biologics license application seeking the approval of lifileucel for the treatment of patients with nonsquamous NSCLC.

References

1. Iovance Biotherapeutics reports potential best-in-class clinical data for lifileucel TIL cell therapy in advanced non-small cell lung cancer (NSCLC). News release. Iovance Biotherapeutics, Inc. November 3, 2025. Accessed November 3, 2025. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-reports-potential-best-class-clinical
2. Autologous LN-145 in patients with metastatic non-small-cell lung cancer. ClinicalTrials.gov. Updated June 26, 2025. Accessed November 3, 2025. https://clinicaltrials.gov/study/NCT04614103?cond=NCT04614103