Lifileucel Confers Durable Responses in Pretreated Advanced NSCLC Type

The receipt of lifileucel (Amtagvi) as monotherapy conferred durable responses among patients with previously treated advanced nonsquamous NSCLC in the registrational phase 2 IOV-LUN-202 trial (NCT04614103), according to a press release from the developer, Iovance Biotherapeutics, Inc.¹

According to interim data from the trial, among 39 patients who were treated, 10 experienced an objective response for an objective response rate (ORR) of 25.6% per RECIST v1.1 criteria. Among responders, 2 attained a complete response (CR), 7 attained a partial response (PR), and 1 had an unconfirmed PR. Furthermore, a disease control rate (DCR) of 71.8% was observed in the trial.

After a median 25.4 months of follow-up, the median duration of response (DOR) was not reached.

The developers plan to present additional data from the trial at an upcoming medical conference in 2026. Additionally, the FDA previously proposed a potency assay matrix to support registration and further provided positive regulatory feedback about the phase 2 study design. Furthermore, in 2026, the trial is expected to progress toward a supplemental biologics license application in the aforementioned population and launch in the second half of 2027.

“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, said in the news release.¹ “One-time treatment with lifileucel monotherapy has the potential to benefit many patients with advanced NSCLC following initial treatment with an immune checkpoint inhibitor.”

The safety profile of the monotherapy was consistent with the underlying disease, non-myeloablative lymphodepletion (NMA-LD), and interleukin-2 (IL-2). Improvements in safety were observed without compromising efficacy after NMA-LD was reduced in this NSCLC population. Specifically, those treated with the updated regimen experienced a reduction in median hospitalization following IL-2 therapy and a lower incidence and duration of cytopenias.

The phase 2 trial enrolled patients with metastatic or unresectable NSCLC without EGFR, ROS1, or ALK actionable genetic mutations who received previous chemotherapy and immune checkpoint inhibition. In the trial, patients underwent a resection for tumor sampling or an image-guided core biopsy, with the sample cultured ex vivo to expand the tumor-infiltrating lymphocyte (TIL) population.² Following lymphodepleting chemotherapy, patients received lifileucel followed by IL-2.

Patients were separated into 5 cohorts: the first treated those who did not express PD-L1, and the second treated those with a PD-L1 tumor proportion score (TPS) of at least 1%. The third cohort treated patients who were unable to undergo surgical resection, and the fourth was open to patients who did not have progressive disease upon tumor sampling but who had documented disease progression at baseline. Cohort 5 was a retreatment cohort for patients previously treated with lifileucel in any of the preceding cohorts.

The primary end point of the study was ORR per RECIST v1.1 criteria in patients with metastatic lung cancer. Secondary end points included ORR in the overall population, CR rate, DOR, duration of CR, and progression-free survival, all per RECIST v1.1 criteria. Additional secondary end points included overall survival and safety.

“Lifileucel has demonstrated a potentially best-in-class clinical profile in previously treated advanced nonsquamous NSCLC. The [DOR] is unprecedented and is combined with an impressive response rate in a one-time monotherapy for a difficult-to-treat patient population,” Friedrich Graf Finckenstein, MD, chief medical officer of Iovance, stated in the press release.¹ “We will pursue regulatory approvals for lifileucel monotherapy to effectively address the tens of thousands of patients with previously treated nonsquamous advanced 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. November 3, 2025. Accessed November 4, 2025. https://tinyurl.com/4en3ra9d
2. Autologous LN-145 in patients with metastatic non-small-cell lung cancer. ClinicalTrials.gov. Updated June 26, 2025. Accessed November 4, 2025. https://tinyurl.com/45jr9jmv