How PDR001 works
Lymphoma is a type of blood cancer. It starts when the body produces too many lymphocytes, or white blood cells, that are part of the immune system. These cells can multiply, travel around the body using the lymphatic system, and clump together to form tumors.
PDR001, an immunotherapy drug, does not directly act on the cancer cells but instead activates the innate immune system and encourages the body to recognize and fight cancer cells.
The immune system normally recognizes and kills infected or abnormal cells, like cancer cells, using lymphocytes called T-cells. In order to stop T-cells from accidentally damaging healthy tissues, immune system checkpoints are in place.
Healthy cells produce and display a protein called PD-L1 or PD-L2 (programmed death ligand 1 or 2) on their surface. T-cells produce a receptor called PD-1. When PD-1 interacts with PD-L1 or PD-L2, it passes a signal to the T-cell, telling it not to attack that cell. This called the PD-1 (programmed death 1) pathway.
Some cancer cells take advantage of these pathways by producing PD-L1 and using it to hide from the T-cells and evade destruction.
PDR001 is an antibody, a protein designed to interact with and block a specific target. It binds to the PD-1 receptor on the surface of the T-cells, preventing them from interacting with PD-L1. This means that T-cells will not receive the message to leave a PD-L1 expressing cell alone, and so will be free to target and destroy the cancer cells.
PDR001 in clinical trials
Novartis is investigating the safety and efficacy of PDR001 in combination with Aduro Biotech’s cancer drug candidate ADU-S100 (or MIW815), in a global Phase 1b study (NCT03172936) in an estimated 175 patients with lymphoma or advanced solid tumors. This follows the U.S. Food and Drug Administration’s June 2017 approval of the company’s investigational new drug application for the combination therapy.
A Phase 2 trial (NCT03207867) is assessing PDR001 in combination with NIR178, one of Novartis’ other cancer drug candidates, in patients with diffuse large B-cell lymphoma (DLBCL) and multiple solid tumors. The trial is currently active and aims to recruit 260 participants.
Novartis is also testing PDR001 in combination with another of its investigational cancer drugs, GWN323, in an open-label Phase 1/1b trial (NCT02740270) in patients with lymphoma or advanced solid tumors. The trial will assess GWN323 alone or in combination with PDR001 in 264 patients.
PDR001 is delivered as a 30-minute intravenous infusion once every four weeks.
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