AGEN2034 is a PD-1 antagonist monoclonal antibody that targets T cell signaling inside the cell. Agenus, the company that developes the drug, announced in April 2017 the beginning of a clinical trial that will assess the safety and effectiveness of the drug in treating cervical cancer.
How does AGEN2034 work?
Programmed death protein 1 (PD-1) is a surface receptor that exists in T cells, which are immune system cells that have the capacity to kill hazardous cells. PD-1 works as a “guardian” against autoimmunity by suppressing the inflammatory activity of T cells.
The issue when it comes to cancer is that when the PD-1 receptor interacts with the programmed death-ligands 1 and 2 (PD-L1 or PD-L2), which can be produced by cancer cells, the T cells’ ability to kill cancer cells is neutralized.
AGEN2034 is an antibody designed to link to PD-1, which blocks the receptor and allows T cells to recognize and kill tumor cells.
Studies of AGEN2034
A Phase 1/2 clinical trial to assess its safety, tolerability, pharmacokinetics, and biological and clinical activity in patients with metastatic or locally advanced solid tumors, with expansion to second-line cervical cancer, is now recruiting an estimated 75 participants in the U.S. (NCT03104699).
The second part of the open-label, dose-escalation trial is planned to evaluate the maximum tolerated dose and the best overall response dose of AGEN2034 in patients with second line cervical cancer.
Agenus is seeking U.S. Food and Drug Administration (FDA) approval for AGEN2034, and to then pursue using it in combination therapies. Agenus is looking to combine AGEN2034 with the CTLA-4 directed antibody already produced by the immuno-oncology company.
Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), like PD-1, is a cell surface receptor with the capacity to down-regulate T cells’ inflammatory effects.
When agenus announced the beginning of the clinical trial, Jean-Marie Cuillerot, MD and chief medical officer, said “Co-targeting the PD-1/PD-L1 axis in combination with CTLA-4 has shown a near doubling of clinical efficacy in certain indications.”