A clinical study aimed at determining whether the experimental drug, called LN-145 (also known as tumor-infiltrating lymphocytes), is safe and beneficial in treating patients with metastatic non-small cell lung cancer.

Descrizione riassuntiva dello studio

There is a need to find new treatments that are more effective than the standard treatments for NSCLC described above. The new drug being studied in this trial is called LN-145. LN-145 is a new type of immunotherapy that uses the body's immune system to destroy cancer cells. LN-145 is made up of T-lymphocytes taken from a fragment of the patient's tumor and multiplied into billions of cells in the laboratory. Once developed, the cells are called "tumor-infiltrating lymphocytes (TILs)." These are administered by infusion, meaning they are slowly injected into a vein (intravenously, "IV") of the patient in question. They are effective at finding and attacking the patient's tumor. Researchers believe that TILs (i.e., the drug product made under the name LN-145) are likely to help treat an NSCLC that has worsened after being treated with chemotherapy, immunotherapy, or targeted therapy. The primary objective of this study is to determine whether LN-145 is capable of reducing the size of a tumor and potentially making it disappear completely. The investigator physician will also check the time that elapses before the development of a tumor and the patient's lifespan after treatment. Another objective of this study is to evaluate the safety of LN-145. A total of 170 patients will participate in this study, distributed across 60 centers worldwide. Patients will participate in the study for a period of up to 5 years after receiving the treatment, provided it is well tolerated, that their cancer does not worsen, and that they wish to continue participating in the study.

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Intervento studiato

This study will consist of 4 periods, described as follows:

 Selection and inclusion (up to 28 days before the start of the study treatment): the investigator physician will check whether each patient meets the requirements to participate in this study. Each patient will be assigned to a treatment group based on specific information related to lung cancer.

 Pre-treatment period (must be completed within 28 days prior to the start of the study chemotherapy, called non-myeloablative lymphodepletion [NMA-LD]): a surgical intervention will be performed to remove a fragment of a tumor, which will be used to manufacture LN-145. The investigator physician will monitor the patient's health status to ensure that their condition is good enough to receive LN-145.

 Treatment period: this period lasts 9 to 10 days. The study treatment begins with 4 days of chemotherapy called NMA-LD. This consists of cyclophosphamide, fludarabine, and mesna. Cyclophosphamide and fludarabine are administered before LN-145 to increase its effectiveness. Mesna is administered to prevent damage caused by cyclophosphamide to the bladder.

There is then 1 day of rest.

Then patients will receive 1 dose of LN-145 by infusion. After that, over a period of 1 to 4 days starting the day after this infusion, a maximum of 6 doses of an immunotherapy called interleukin-2 (IL-2) will be administered by infusion. Patients will remain in the hospital, including overnight, during the treatment period. They may be asked to stay in the hospital a little longer if necessary.

 Post-treatment period (up to 5 years): after treatment, tumor examinations, general medical tests, clinical examinations, and other examinations and analyses will continue to be performed on patients, approximately every 6 weeks until Month 6, then every 3 months until Month 22, and then every 6 months until the end-of-study visit, if their cancer does not worsen and no new anticancer treatment has been initiated. Patients will be contacted every 3 months until the end-of-study visit, for a total of 5 years (60 months) after receiving LN-145.

Dosage of medications in the 3 parts:

1. NMA-LD: cyclophosphamide 20 mg/kg, fludarabine 25 mg/m2, and mesna (standard dose, administered to prevent damage caused by cyclophosphamide to the bladder)

2. Infusion of LN-145: dose prepared for each patient, approximately 100 to 125 ml of cells in a cryopreservation bag; total dose between 1 x 10^9 and 150 x 10^9 viable cells in total for IV infusion. Depending on the number of cells, a maximum of four bags will be provided to the center

3. IL-2: interleukin 600,000 UI/kg.

What are the benefits and risks associated with this study?

Patients may or may not benefit from LN-145. Although the sponsor (Iovance Biotherapeutics) hopes that LN-145 will be helpful for patients with NSCLC, it is still unknown whether this will be the case. The information gathered in this study will help the sponsor learn more about this new drug and will also help future patients with NSCLC.

Like all medications, there is a risk that the study treatment may cause unwanted effects, known as "adverse effects." Patients may experience adverse effects and/or discomfort during their participation in the study, including some unknown adverse effects. There are also adverse effects associated with the other treatments that patients will receive as part of this study (cyclophosphamide, fludarabine, and IL-2), and there may also be risks associated with treatments prescribed by the investigator physician to manage the adverse effects of chemotherapy.

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Malattie studiate

Metastatic non-small cell lung cancer (NSCLC) that has worsened after being treated with chemotherapy, immunotherapy, or targeted therapy / The health status is acceptable to receive autologous tumor-infiltrating lymphocyte (TIL) therapy; Cancer is a disease in which some cells divide uncontrollably and form tumors. Researchers want to find better ways to treat a common type of lung cancer called non-small cell lung cancer (NSCLC). Normally, a type of white blood cell (T-lymphocytes) tries to find and destroy cancer cells before they have developed to the point that a doctor notices them. T-lymphocytes are part of the immune system. Cancer cells can make special proteins that help them hide from T-lymphocytes and continue to grow. Among the ways to treat NSCLC are standard chemotherapy, immunotherapy, targeted therapy, or a combination of these different treatments. Standard chemotherapy involves using powerful chemicals to destroy cancer cells; it can cause serious side effects. Immunotherapy involves using substances that stimulate the body's immune system to help fight cancer. Targeted therapy uses drugs to target specific substances in the body that help cancer cells survive and spread. It may happen that these treatments stop being effective.

(BASEC)

Sponsor

PPD Switzerland GmbH c/o Dufour Treuhand AG

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Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)

Commissione d'etica Vaud

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Data di approvazione del comitato etico

10.10.2024

(BASEC)

Risultati dello studio