cphi-onlineMay 21, 2021
Tag: American Society of Clinical Oncology (ASCO) , NC410 , NextCure
NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases, today announced that clinical trial investigator, Martin Gutierrez, M.D., Director, Phase 1 Program and Co-Chair of Thoracic Oncology at Hackensack University Medical Center, will present a Trials in Progress poster for NC410 at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
"NC410 targets a unique mechanism in the tumor microenvironment (TME) and represents an innovative approach for patients who do not respond to current available therapies by targeting tumors with collagen-rich areas where LAIR-1+ immune cells localize," said Dr. Gutierrez. "LAIR-1 expression on immune cells in the TME inhibits T cell responses, through binding to collagen therefore leading to tumor growth. NC410 is designed to act as a LAIR-1 decoy to prevent LAIR-1 mediated immunosuppression. This leads to restoration of immune function as evidenced by increased production of several cytokines, and anti-tumor responses in preclinical models. I look forward to a continued collaboration with NextCure to advance this product through the clinic."
"We are excited to discuss our rationale for developing NC410 as a first-in-class cancer therapeutic targeting the LAIR pathway as well as our Phase 1/2 clinical trial strategy with the clinical oncology community at ASCO," said Han Myint, M.D., NextCure's chief medical officer. "NC410 demonstrates anti-tumor activity in preclinical models, and we believe it has significant potential across multiple tumor types, including gastric, ovarian, lung head and neck. We look forward to continuing to evaluate NC410 in first-in-human trials and reporting initial clinical data in the second half of 2021."
Collagens are a primary component of the extracellular matrix (ECM) in the TME and are functional ligands for the inhibitory immune receptor leukocyte associated immunoglobulin-like receptor (LAIR)-1. LAIR-1 binding to collagens suppresses anti-tumor immunity through the inhibition of key stimulatory signaling pathways. NC410 is designed as a fusion protein of LAIR-2, a soluble homolog of LAIR-1 fused to human IgG1 Fc domain, and it acts as a LAIR-1 decoy by binding collagen with higher affinity than LAIR-1 to prevent LAIR-1 mediated immunosuppression and promoting anti-tumor response. Because NC410 binds to collagen rich areas, it also induces alterations in the ECM to promote immune cell infiltration and function in the TME. LAIR-1 expression has been observed across tumor types, including non-small lung cancer (NSCLC), gastric, colorectal, pancreatic, ovarian and head & neck cancers. In this trial we plan to evaluate the measurement of collagen fragments in serum as potential biomarkers to non-invasively interrogate cell reactivity in the TME and predict response to treatment, which may be important for patient stratification for the Phase 2 portion of the study.
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