TG-1501 (cosibelimab) is an investigational fully humanized monoclonal antibody that binds to the programmed death-ligand 1 (PD-L1) and blocks its interactions with PD-1. It has been well established that cancer cells can evade anti-tumor immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Signals from PD-L1 on tumor cells and in the tumor microenvironment help those tumors avoid immune mediated elimination by preventing activation of tumor-specific effector T-cells. Anti-PD-L1 antibodies are designed to block that signal, permitting effector T-cells to attack and kill the cancer.
Despite the demonstrated activity of anti-PD-L1and PD-1 therapy across a variety of cancers, there is limited clinical trial experience with this class of drugs across different types of B-cell cancers such as Non-Hodgkin’s Lymphoma (NHL) and chronic lymphocytic leukemia (CLL), which is the focus of our team.
Preclinically, it has been shown that the effects of anti-PD-L1 can be enhanced by complementing other mechanisms in the tumor microenvironment, like targeting CD20 and CD47 for example, which may render the malignant cells more vulnerable to the host immune system. Based on this preclinical data, we are exploring combination regimens in an effort to optimize the effects of the anti-PD-L1 antibodies against lymphoma and CLL.
A phase 1 trial in the United States is evaluating TG-1501 alone and in combination with umbralisib and ublituximab in patients with CLL and NHL.