Abstract P3-12-30: Phase I trial of pegylated liposomal doxorubicin chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic HER2 negative breast cancer

作者：Sangeetha M. Reddy, Cesar A. Santa‐Maria, Virginia Kaklamani, Joyce O’Shaughnessy, Nisha Unni, Navid Sadeghi, Samira Syed, Joshua J. Gruber, Yisheng Fang, Isaac S. Chan, Namrata Peswani, Shahbano Shakeel, Meredith Carter, Kelly Kyle, Dawn Klemow, Nan Chen, Rita Nanda, Heather L. McArthur, Suzanne D. Conzen, Carlos L. Arteaga · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1557-3265.sabcs24-p3-12-30 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、Cancer Treatment and Pharmacology

Abstract Background: Only a subset of patients with metastatic breast cancer respond to FDA approved immune checkpoint blockade, and few have durable responses. Data suggest that breast cancers have defects in antigen presentation and that antigen presenting dendritic cells (DCs) are required for response to T cell directed immunotherapies such as immune checkpoint blockade. CD40 agonists activate antigen presenting cells, including DCs and B cells, and repolarize macrophages to an anti-tumor phenotype. Flt3 ligand is a growth factor that increases differentiation and expansion of DCs. We recently demonstrated in pre-clinical breast cancer models that the combination of liposomal doxorubicin chemotherapy, a CD40 agonist, and a Flt3 ligand improves outcomes compared to chemotherapy alone.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. Patients are randomized to 2 lead-in arms in 2:1 ratio (triplet therapy or liposomal doxorubicin only) for one cycle prior to receiving triplet therapy with tumor biopsies done before and after the lead-in treatment. A recent protocol amendment expanded eligibility from triple negative breast cancer (TNBC) to also include hormone receptor positive (HR+) breast cancer and closed a lead-in cohort of immunotherapy only. CDX-301 will ...