Immunotherapies have improved the survival of people who have a variety of cancers. However, these therapies have shown limited activity in some tumors, such as those found in pancreatic and colorectal cancers and sarcomas. Kristen Spencer, DO, MPH, is leading a clinical trial at NYU Langone Health’s Perlmutter Cancer Center to evaluate an experimental agent called CDX-585, a bispecific antibody that targets two different cell types in solid tumors.
CDX-585 targets PD-1, a protein found on T cells, and ILT4, an immunosuppressive molecule predominantly expressed on myeloid cells. PD-1 and ILT4 have been associated with poor clinical outcomes in several cancer types. Some studies have suggested that activation of ILT4 serves as a resistance mechanism for blockade of PD-1 and its ligand PD-L1, which are the targets of immunotherapies such as pembrolizumab (Keytruda) and nivolumab (Opdivo).
“Bispecific antibodies—therapies that contain antibodies that target different immune receptors simultaneously—are an exciting concept in cancer treatment,” said Dr. Spencer, an associate professor in the Department of Medicine at NYU Grossman School of Medicine and director of the Phase 1 Developmental Therapeutics Program at Perlmutter Cancer Center. “This particular compound inhibits both T cells and myeloid suppressive cells, which is a cell type that we are beginning to understand more in terms of their role in suppressing a response to immunotherapy.”
This open-label, multicenter study of CDX-585 is being evaluated in people with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. Perlmutter Cancer Center is the first and only site activated for this study. The first patient was dosed at the end of May.
“Targeting two different cell types within these tumors might enable us to overcome resistance to immune medications in patients where they haven’t been overly effective so far and expand eligibility for immune medications to include more people with solid tumors,” Dr. Spencer said.