Phase II study of NC410 and FOLFIRINOX in combination with nivolumab with or without ipilimumab in patients with treatment-naive metastatic pancreatic cancer.

作者：Shriram K. Sundararaman, Beth Onners, Brad Wilt, Hao Wang, Ewa Kulikowicz, Song Truong, Soren Charmsaz, Alexei Hernandez, Jennifer N. Durham, Dan Laheru, Elizabeth M. Jaffee, Won Jin Ho, Dung T. Le, Katherine M. Bever · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.tps4260 · 研究领域：Complement system in diseases、CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers

TPS4260 Background: Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer-related death in the United States (1). Median overall survival for patients with metastatic PDAC is 11.1 months with first-line FOLFIRINOX chemotherapy (2) and more effective treatments are needed. A major resistance mechanism to immunotherapy in PDAC is the desmoplastic stroma (3). Collagen physically hinders T cell infiltration and suppresses immune cells in the tumor microenvironment (TME) through the Leukocyte Associated Immunoglobulin-like Receptor-1 (LAIR-1) (4). Both collagen and the complement protein C1q, overexpressed in the PDAC TME, are primary ligands for the inhibitory LAIR-1 receptor on myeloid and lymphoid cells, and binding results in immune cell downregulation (5-7). LAIR-2, primarily made by CD4+ T cells, is a competitive inhibitor of LAIR-1 that reverses the immunosuppressive effect (8). NC410 is a dimeric fusion protein of LAIR-2 with human IgG1 Fc that remodels collagen, reduces tumor growth, enhances T cell tumor infiltration, and overcomes neutrophil-mediated T cell suppression in preclinical studies (7,9,10). NC410 binds the collagen-rich PDAC TME with high avidity when compared across tumor types (7). Our group contributed to the recent phase Ib/II study demonstrating clinical activity of NC410 with pembrolizumab in patients with advanced colorectal and ovarian cancer (NCT05572684). Based on these promising results, our study combines NC410 and immunotherap...