NEW YORK – NGM Bio on Thursday announced the start of a Phase I/Ib trial of its myeloid checkpoint inhibitor, NGM438, in patients with advanced solid tumors.
NGM438 is NGM's third myeloid reprogramming product to enter clinical trials. The other drugs are NGM707, a dual ILT2/ILT4 antagonist antibody, and NGM831, an ILT3 antagonist antibody. The firm will advance all three therapies with a biomarker strategy for target engagement, dose selection, proof of mechanism, and potentially, patient selection.
NGM believes its pipeline of myeloid checkpoint inhibitors may serve as an alternative to T-cell checkpoint inhibitors, to which only 20 percent to 30 percent of patients respond. Myeloid cells are present in the tumor microenvironment and studies have shown that they play a role in suppressing the immune response to the tumor. NGM's portfolio of antagonist antibody drugs are targeted to receptors associated with poor responses to T-cell checkpoint inhibitors.
NGM438 is an antibody designed to inhibit LAIR1, which is upregulated in multiple types of cancer. In a preclinical study, NGM found that blocking LAIR1 with NGM438 and anti-PD-1 antibodies diminished tumor growth in a mouse model.
The recently launched Phase I/Ib trial will enroll up to 80 patients with solid tumors including pancreatic, colorectal, ovarian, non-small cell lung, and other cancers. The Phase I portion of the trial will explore escalating doses of NGM438 monotherapy, proceeding to the Phase Ib dose-finding portion with Merck's Keytruda (pembrolizumab).
The study also contains a part Ic, which NGM has dubbed the "serial tumor biopsy biomarker cohort," in which patients will receive NGM438 for one cycle, then undergo a tumor biopsy followed by NGM438 with Keytruda. The firm will evaluate patients' tumor biopsies for changes in three biomarkers: CD163, MMP9, and CD8.
The South San Francisco, California-based firm's other drug, NGM707, is undergoing a Phase I/II trial involving patients with advanced solid tumors with elevated expression of ILT2 and ILT4. In December 2021, NGM inked a deal with Merck to study NGM707 with Keytruda. NGM831, meanwhile, is in a Phase Ia/Ib trial in patients with advanced or metastatic solid tumors.