Abstract PS5-08-28: Phase I pilot of pegylated liposomal doxorubicin, CD40 agonist antibody CDX-1140, and Flt3 ligand CDX-301 in advanced HER2-negative breast cancer

作者：S. M. Reddy, C. A. Santa-Maria, N. Chen, V. Kaklamani, J. O’Shaughnessy, Y. Abdou, N. Unni, B. Santos, S. Syed, Navid Sadeghi, J. Gruber, Dawn Klemow, Y. Fang, Ivan S. F. Chan, Namrata Peswani, I. Patel, Shahbano Shakeel, M. Carter, Kelly Kyle, R. Nanda, H. McArthur, S.D. Conzen, C. L. Arteaga · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1557-3265.sabcs25-ps5-08-28 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、HER2/EGFR in Cancer Research

Abstract Background: Immune checkpoint inhibitors deliver durable benefit to only a minority of individuals with metastatic breast cancer, in part due to a paucity of activated, antigen-presenting dendritic cells within the tumor microenvironment. Pre-clinical work from our group showed that combining pegylated liposomal doxorubicin (to release tumor antigens) with a CD40 agonist (to license dendritic cells and repolarize macrophages toward an anti-tumor phenotype) and recombinant Flt3 ligand (to expand dendritic cell precursors) produces markedly superior tumor control compared with chemotherapy alone. These findings underpin the first-in-human clinical evaluation of this triplet regimen. Methods: This is a single arm phase I pilot study of the combination of liposomal doxorubicin, CDX-1140 (CD40 agonist monoclonal antibody), and CDX-301 (recombinant Flt3 ligand) in patients with metastatic or unresectable locally advanced HER2 negative breast cancer (triple negative, TNBC; and hormone receptor positive, HR+). Two lead-in cohorts randomize participants in a 2:1 ratio to receive one cycle of either the triplet combination or pegylated liposomal doxorubicin alone, after which all patients transition to triplet therapy; paired tumor biopsies are obtained at baseline and after the lead-in to characterize early immunological changes. Eligibility originally limited enrollment to triple-negative disease but has been broadened to include HR+ tumors. Key eligibility criteria are unre...