A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors

More details:

Overview

LN-145 (lifileucel) is a personalized tumor-infiltrating lymphocyte (TIL) therapy. It remains investigational for cervical cancer and other uses, but is FDA-approved in the United States as Amtagvi for certain adults with unresectable or metastatic melanoma after prior treatment. The melanoma indication received accelerated approval in February 2024; continued approval may depend on a trial confirming clinical benefit. (ascopubs.org)

Mechanism of action

T cells are collected from a patient’s tumor, expanded outside the body, and infused back into the patient to attack cancer cells. Treatment also includes chemotherapy to reduce existing lymphocytes before infusion and interleukin-2 afterward to support the infused cells. Rather than targeting one specified molecule, the product contains a mixture of tumor-derived T cells. (pubmed.ncbi.nlm.nih.gov)

Efficacy

• Melanoma: In the single-arm phase 2 study supporting approval, 23 of 73 patients (31.5%) responded, including three complete responses. Median response duration had not been reached at the FDA’s analysis. A later five-year analysis of a broader 153-patient study population reported a 31.4% response rate and a median response duration of 36.5 months. These were not comparisons against another treatment. (aacrjournals.org)
• Cervical cancer: An early phase 2 conference abstract reported a 44% response rate among 27 previously treated patients. This small, uncontrolled result is preliminary and does not establish benefit in cervical cancer. (ascopubs.org)

Safety

Treatment can cause serious harm. Across 156 lifileucel-treated patients in the melanoma study’s primary and supportive cohorts, 95.5% experienced a grade 3 adverse event and 87.8% a grade 4 event. The U.S. prescribing information carries a boxed warning for treatment-related death, prolonged severe low blood-cell counts, severe infection, and heart, lung, or kidney impairment. These risks are assessed in the context of the whole treatment regimen, including lymphodepleting chemotherapy and interleukin-2. (aacrjournals.org)

Further reading

• FDA approval summary and trial analysis
• Five-year melanoma study results
• Cervical cancer phase 2 conference abstract

Last updated: Sep 2026

Overview

LN-145-S1 (PD-1 Selected TIL) is an investigational, patient-derived tumor-infiltrating lymphocyte (TIL) therapy. It has been studied in a phase 2 trial in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) and included in a separate phase 2 study of solid tumors. Results from LN-145, a different TIL product, should not be attributed to LN-145-S1. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

T cells are collected from a patient’s tumor, selected for expression of PD-1, expanded outside the body, and infused back into the patient after lymphodepleting chemotherapy; interleukin-2 is given afterward. PD-1 selection is intended to enrich for tumor-reactive T cells. PD-1 is therefore a selection marker for this product, not a molecular target blocked by LN-145-S1. (cdn.clinicaltrials.gov)

Efficacy

In the LN-145-S1 cohort of the non-randomized HNSCC trial, 2 of 12 treated patients (17%) had a partial response; none had a complete response. Seven more had stable disease, yielding a disease-control rate of 9 of 12 (75%). The two partial responses lasted 7.6 and 12.9 months as reported in the study. The small cohort and lack of a control group limit conclusions about benefit. (jitc.bmj.com)

Safety

The HNSCC study reported two deaths from respiratory failure in the 12-patient LN-145-S1 cohort, occurring 7 and 16 days after infusion. The authors stated that one was not related to LN-145-S1; their report also described a grade 3 infusion-related reaction in one cohort patient. Adverse effects must be interpreted in the context of the full treatment regimen, which included lymphodepleting chemotherapy and interleukin-2. (jitc.bmj.com)

Further reading

• Peer-reviewed HNSCC trial report
• Phase 2 solid-tumor study abstract

Last updated: Sep 2026

Inclusion Criteria

* Must have a confirmed diagnosis of malignancy of their receptive histologies: unresectable or metastatic melanoma Stage IIIC to IV (Cohorts 1A,1B and 1C), advanced, recurrent or metastatic HNSCC (Cohort 2A), or Stage III or Stage IV non-small cell lung cancer (Cohorts 3A, 3B, and 3C). Stage IV NSCLC with no actionable mutations (EGFR, ALK, ROS1) with effective targeted therapy (Cohorts 3D and 3E).

* Cohorts 1A, 1D, 2A, 3A, 3D and 3E: If previously treated, patients must have progressed on or after most recent therapy and must not have received ICIs as part of one of the counted lines of prior therapy. Patients must have radiologically documented disease progression while receiving or after the completion of the most recent prior treatment. Patients may have received up to 3 prior systemic anticancer therapies (except for Cohort 3A, where patients whose tumors harbor actionable mutations may have received up to 4 prior systemic therapies). Patients in Cohort 1D may have had no prior therapy for advanced disease. Patients in Cohorts 3D and 3E may have had no prior systemic therapy for Stage IV disease.

* Cohorts 1B, 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts 1B or 1C must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients in Cohort 3B must have previously received systemic therapy with any ICI (except for those patients with known oncogene driver mutations that are sensitive to targeted therapies) as part of 1 - 3 prior lines of therapy. NSCLC patients in Cohort 3C must have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neoadjuvant settings are allowed.

* Must have at least 1 resectable lesion

* Must have remaining measurable disease as defined by RECIST 1.1 following tumor resection

* Must be ≥ 18 years at the time of consent for Cohorts 1A, 1C, 1D, 2A, 3A, 3B, 3C, 3D and 3E. Patients must be ≥ 12 years at the time of consent for Cohort 1B. Enrollment of patients \> 70 years of age may be allowed after consultation with the Medical Monitor.

* Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an estimated life expectancy of ≥ 6 months.

* Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of birth control during treatment and for 12 months after their last dose of aldesleukin, 4 months after their last dose of pembrolizumab, 5 months after their last dose of ipilimumab or nivolumab, or nivolumab-relatlimab; 6 months after the last dose of carboplatin; 14 months after the last dose of cisplatin; and 6 months after the last dose of pemetrexed, paclitaxel, or nab-paclitaxel, whichever occurs later.

Exclusion Criteria

* Patients with melanoma of uveal/ocular origin.

* Patients who have a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. Patients being retreated with TIL, as part of this study are not excluded.

* Patients who have symptomatic, untreated brain metastases or history of leptomeningeal metastases.

* Patients who are on systemic steroid therapy \> 10 mg/day of prednisone or other steroid equivalent. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent may be eligible.

* Patients who are pregnant or breastfeeding.

* Patients who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation

* Cohort 1A, 1D, 2A, 3A, 3C, 3D and 3E patients may not have a medical history of autoimmune disorders (including pneumonitis) requiring treatment or active management.

* Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment

* Patients who have any form of primary immunodeficiency

* Patients with a history of hypersensitivity to any component of the study drugs to be administered in the pertinent cohort(s).

* Patients who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association Class II or higher. A cardiac stress test demonstrating any irreversible wall movement abnormality in any patients ≥60 years of age or in patients who have a history of ischemic heart disease, cardiac chest pain, or clinically significant atrial and/or ventricular arrhythmias.

* Patients with respiratory dysfunction or history of smoking are excluded if not meeting either of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) \> 0.7 or FEV1 \> 50%.

* Patients who have had another primary malignancy within the previous 3 years

* Participation in another interventional clinical study within 21 days prior to the initiation of treatment.

* Patients in Cohorts 1D, 3D, or 3E who previously received adjuvant or neoadjuvant ICI(s) for non-metastatic disease and had an immune-related AE(s) requiring systemic steroid treatment or discontinuation of immune checkpoint inhibitor therapy.