NEW YORK – NGM Biopharmaceuticals and Merck on Monday entered into a clinical trial collaboration and supply agreement to evaluate NGM's ILT2/4 dual antagonist antibody NGM707 with pembrolizumab (Merck's Keytruda) in patients with advanced or metastatic solid tumors with elevated expression of ILT2 and ILT4.
The Phase I portion of the study will involve up to 60 patients, who will be enrolled in either an NGM707 monotherapy arm or a dose-finding NGM707-pembrolizumab combination arm. The Phase II part of the study will have a basket design and explore the activity of NGM707 monotherapy and NGM707-pemobrolizumab in another 120 patients with various solid tumors.
NGM707 is designed to inhibit both the ILT2 and ILT4 receptors, which can contribute to resistance to checkpoint inhibitors. In preclinical models of NGM707 plus pembrolizumab, the combination showed increased T-cell activation and cytokine secretion, Hsiao Lieu, NGM's chief medical officer, said in a statement.
"ILT2 and ILT4 are among a group of myeloid immune checkpoint receptors that are upregulated in patients who do not respond to T-cell checkpoint therapy, suggesting that they are potential resistance mechanisms that generate an immunosuppressive state in the tumor microenvironment," Lieu continued. "Our preclinical studies suggest that NGM707's dual blockade of ILT2 and ILT4 may be more effective than blockade of either receptor alone in reversing myeloid based immune suppression, which is known to limit anti-tumor immunity."
NGM, based in South San Francisco, California, is also developing other myeloid checkpoint inhibitor candidates, including drugs targeting ILT3 and LAIR1 that are in preclinical studies.