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

Lifileucel (also known as LN-145) is an autologous tumor-infiltrating lymphocyte (TIL) therapy developed for the treatment of advanced cancers, particularly in patients who have progressed after standard treatments. It involves harvesting TILs from a patient's tumor, expanding them ex vivo, and reinfusing them to target cancer cells.

Mechanism of Action

Lifileucel utilizes a patient's own TILs, which are immune cells that have naturally infiltrated the tumor. By expanding these cells outside the body and reinfusing them, the therapy aims to enhance the body's immune response against cancer cells. This approach leverages the TILs' ability to recognize and attack tumor-specific antigens.

Efficacy

Metastatic Melanoma:

In a Phase II, open-label, single-arm, multicenter study involving 66 patients with advanced melanoma who had progressed after immune checkpoint inhibitors and, if applicable, BRAF/MEK inhibitors, lifileucel demonstrated:

• Objective Response Rate (ORR): 36% (95% CI, 25% to 49%), including 2 complete responses and 22 partial responses.
• Disease Control Rate: 80% (95% CI, 69% to 89%).
• Duration of Response: Median not reached after a median follow-up of 18.7 months.

These results suggest that lifileucel offers durable responses in heavily pretreated melanoma patients. (ascopubs.org)

Non–Small Cell Lung Cancer (NSCLC):

A Phase II multicenter study evaluated lifileucel in 28 patients with metastatic NSCLC who had progressed after prior immunotherapy. The findings included:

• ORR: 21.4% (6 out of 28 patients).
• Notable Responses: Observed in tumors typically resistant to immunotherapy, such as PD-L1–negative and low tumor mutational burden tumors.

These results indicate potential efficacy in a challenging patient population. (pubmed.ncbi.nlm.nih.gov)

Safety

The safety profile of lifileucel is consistent with known adverse events associated with nonmyeloablative lymphodepletion and interleukin-2 administration. Common Grade 3/4 treatment-emergent adverse events include:

• Thrombocytopenia: 76.9%
• Anemia: 50.0%
• Febrile Neutropenia: 41.7%

In the NSCLC study, two patients experienced treatment-emergent adverse events leading to death: cardiac failure and multiple organ failure. Overall, adverse events were generally manageable and as expected for this type of therapy. (pubmed.ncbi.nlm.nih.gov)

Further Reading

• Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
• Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non–Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors

Last updated: Apr 2025

Overview

LN-145-S1, also known as PD-1 Selected TIL, is an investigational therapy involving tumor-infiltrating lymphocytes (TILs) selected for low PD-1 expression. This approach aims to enhance the efficacy of TIL therapy by enriching for T cells with potentially higher antitumor activity.

Mechanism of action

The therapy involves isolating TILs from a patient's tumor, selecting those with low PD-1 expression, expanding them ex vivo, and reinfusing them into the patient. PD-1 is an inhibitory receptor that can dampen T cell responses; selecting TILs with low PD-1 expression may enhance their ability to attack tumor cells.

Clinical trials

As of now, there are no publicly available results from clinical trials evaluating the efficacy and safety of LN-145-S1 in humans. Further research is needed to determine its therapeutic potential.

Further reading

• Tumor-Infiltrating Lymphocytes (TIL) Therapy

Last updated: Apr 2025

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.