TIL Cell Therapy Lifileucel Makes Efficacy, Safety Gains in Advanced NSCLC

Positive interim data from the phase 2 IOV-LUN-202 study (NCT04614103) evaluating the autologous tumor-infiltrating lymphocyte (TIL) cell therapy lifileucel (LN-145; Amtagvi) show durable responses and an improved safety profile in pretreated patients with advanced nonsquamous non–small cell lung cancer (NSCLC).¹

At a median follow-up of 25.4 months, a 25.6% objective response rate (ORR) and 71.8% disease control rate was observed in patients who were treated with one-time lifileucel monotherapy. Of 39 patients, 10 objective responses were observed, including 2 complete responses (CRs), 7 partial responses (PRs), and 1 unconfirmed PR.

“Lifileucel has demonstrated a potentially best-in-class clinical profile in previously treated advanced nonsquamous NSCLC. The duration of response is unprecedented and is combined with an impressive response rate in a one-time monotherapy for a difficult-to-treat patient population,” said Friedrich Graf Finckenstein, MD, chief medical officer of Iovance Biotherapeutics, in a news release.¹

Regarding safety, lifileucel’s safety profile was consistent with the known safety profiles of non-myeloablative lymphodepletion (NMA-LD) and interleukin-2 (IL-2). Improvements in safety without compromising efficacy were noted after a regimen update, with a reduction of median post-IL-2 hospitalization days by more than half. These safety results are encouraging given that the trial faced a temporary setback in 2024 due to a patient death potentially related to the NMA-LD preconditioning regimen, resulting in a clinical hold by the FDA.

About the IOV-LUN-202 Trial

The IOV-LUN-202 trial is a global, prospective, open-label, nonrandomized phase 2 study evaluating the performance of lifileucel monotherapy in adult patients with metastatic or unresectable NSCLC who have been previously treated with an immune checkpoint inhibitor.² The study’s primary end point is ORR; secondary end points include CR rate, duration of response, disease control rate, progression-free and overall survival, safety, and core biopsies.

The study is actively recruiting and estimated to enroll 170 patients with histologically or pathologically confirmed metastatic stage IV NSCLC without EGFR, ROS, or ALK mutations. Patients must have had disease progression following at least 1 prior line of therapy.

Next Steps in Development

Looking ahead, the sponsor announced that additional data from the trial will be presented at an upcoming medical meeting next year.

Further, positive regulatory feedback from the FDA has concluded an alignment with single-arm trial design supporting accelerated approval, enabling advancement toward potential registration.

“We will pursue regulatory approvals for lifileucel monotherapy to effectively address the tens of thousands of patients with previously treated nonsquamous advanced NSCLC,” added Finckenstein regarding next steps in the news release.¹

The phase 2 trial is expected to progress throughout 2026 and complete in the latter half of the year, at which point the sponsor intends to pursue a supplemental biologics license application (sBLA) for lifileucel in nonsquamous NSCLC.

In February 2024, lifileucel was granted accelerated approval by the FDA for treatment adult patients with advanced melanoma, designating the agent as the first FDA-approved T cell therapy for a solid tumor indication.³ Approval of the sBLA would expand the therapy’s application to its first lung cancer indication characterized by treatment resistance and high unmet need.

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. November 3, 2025. Accessed November 3, 2025. https://tinyurl.com/yeywrfrj

2. Autologous LN-145 in patients with metastatic non-small-cell lung cancer. ClinicalTrials.gov. Updated June 25, 2025. Accessed November 3, 2025. https://clinicaltrials.gov/study/NCT04614103

3. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. US Food & Drug Administration. Updated February 16, 2024. Accessed November 4, 2025. https://tinyurl.com/mr2j54ck