GWN323 is an investigational immunotherapy being developed by Novartis to treat patients with certain advanced solid tumors and lymphomas. A monoclonal antibody, GWN323 targets a receptor on a type of immune cell called T-cells to stimulate the immune system to attack cancer cells.

How GWN323 works

GWN323 is an antibody that binds to the human glucocorticoid-induced tumor necrosis factor receptor (or GITR), a receptor expressed on the surface of many different types of T-cells. When GWN323 binds to GITR, it stimulates the immune system to increase the activity of T-effector (Teff) cells and suppress the activity of T-regulatory (Treg) cells.  Tregs act to suppress the immune response, while Teffs actively participate in the immune response to help fight invaders.

Shifting the balance of Teff and Treg cells can increase the activity of the immune system, making it more effective in fighting and destroying cancer cells.

Preclinical studies in mice showed that combining anti-GITR with checkpoint inhibitors improved anti-tumor activity in the animals and their overall survival. Checkpoint inhibitors enhance immune activity by targeting proteins that suppress the immune response, essentially giving the immune system a “green light” to attack tumors.

GWN323 in clinical trials

A ongoing Phase 1/1b open-label, multicenter trial (NCT02740270) is testing GWN323 in patients with advanced solid tumors and lymphomas. Participants are being given either GWN323 alone or GWN323 in combination with another experimental drug, the checkpoint inhibitor PDR001.

The trial’s first part is a dose escalation study to determine the highest dose that can be safely tolerated, called the maximum tolerated dose (MTD), and the second part will be an expansion trial, which will use the dose established in part 1 to find out how safe and effective GWN323 is both alone and in combination with PDR001.

The trial, which began in 2016 and is expected to conclude in May 2019, expects to enroll about 264 adults and is still recruiting patients at sites across the U.S., in Ontario, Canada, and in Israel, Singapore and Spain.

Additional information

Therapy with GWN323 and other immunotherapies — drugs that activate the immune system to fight cancer — can cause side effects referred to as immune-related adverse events (IRAEs). When the immune system is stimulated and normal checkpoints are suppressed, autoimmune-type responses can result. In these responses, immune cells attack healthy organs, including the skin (causing rashes), liver, bowel, and endocrine glands.

IRAEs are not true autoimmune diseases, because these reactions usually stop when the patient is taken off the immunotherapy.


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