LAG525 (anti-LAG-3, also known as IMP701) is an investigational immunotherapy being developed to potentially treat a range of solid tumors.
Development of LAG525 began under Immutep S.A. and is now being continued by Novartis in collaboration with the Australian biotechnology company Prima BioMed.
How LAG525 works
As a type of immunotherapy, LAG525 works to boost the body’s immune response against cancer rather than acting on a tumor itself. The immune system can identify abnormal cells, including cancer cells, and work to kill them by activating specialized immune cells called T-cells.
LAG525 is an antibody, or a protein is designed to bind to a specific target against the lymphocyte activation gene-3 (LAG-3, also known as CD223). Lymphocytes are a type of white blood cell. This gene has multiple roles in the immune system, including that of an immune system checkpoint — a signaling pathway designed to inhibit T-cells so they do not damage healthy cells.
The cell-surface protein LAG-3 is produced by activated T-cells and, when it interacts with another group of proteins called MHC class 2, inhibits the cell-killing ability of T-cells. LAG-3 can also reduce T-cell growth and activation.
When LAG525 binds to LAG-3 on T-cells present in the tumor, it blocks LAG-3 from interacting with MHC class 2. This should allow T-cells to continue proliferating and targeting the cancer cells, resulting in a reduction in tumor growth or size.
LAG525 in clinical trials
Novartis is currently running an open-label Phase 1/2 clinical trial (NCT02460224) to assess the safety and efficacy of LAG525, alone and in combination with another investigational immunotherapy called PDR001. The trial aims to recruit 421 patients with advanced solid tumors at 21 sites across North America, Europe, Australia, and Asia. More information is available by clicking on the trial’s identification number.
The study’s Phase 1 portion consist of giving patients escalating doses to determine the maximum tolerated dose of LAG525 (alone and in combination with PDR001). Patients will be monitored for up to 30 months to record adverse events potentially caused by the treatment.
The Phase 2 portion will make a preliminary assessment of the treatment’s anti-tumor activity by measuring the overall response rate over 30 months. The trial is expected to end in April 2019.
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