NCI-2025-06021

Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer (TRIPL)

This is a research study exploring how combining radiation therapy with dual immune checkpoint inhibition can improve outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). This study focuses on patients whose cancer cannot be surgically removed but has not yet spread beyond the chest. It tests whether adding inhibitors of PD-1 (Programmed Death-1) and LAG-3 (Lymphocyte-Activation Gene-3) — two proteins that suppress immune system activity — can enhance the immune response triggered by thoracic radiotherapy. Radiation not only shrinks tumors directly but can also release tumor antigens that help the immune system recognize cancer cells; the checkpoint inhibitors are intended to keep the immune system “switched on” to sustain that response. The goal is to determine if this combination can make treatment more effective and potentially more durable compared to standard chemoradiation or immunotherapy alone.

Check point inhibitor: The immune system can help fight cancer. Drugs called “checkpoint inhibitors” work by releasing a natural brake on your immune system so that immune cells can recognize and attack tumors.

non-small cell lung cancer (NSCLC): A type of lung cancer with non small cells that grow too much and can spread to other parts of the body

PD-1: PD-1 is a protein found on T cells (a type of immune cell) that helps keep the body’s immune responses (defense system) in check. When this protein is blocked, the “brakes” on the immune system are released and the ability of T cells to kill cancer cells is increased.

For more information about the trial, click the link below:

https://clinicaltrials.gov/ct2/show/NCT06865339

Clinical Trial Site: Einstein - Radiation

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