Phase 1 pilot study with dose expansion of chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer.

作者：Sangeetha M. Reddy, Meredith Carter, Isaac S. Chan, Melanie Hullings, Nisha Unni, Jessica Medina, Shahbano Shakeel, Susan Armstrong, Lakeisha Cade, Farjana Fattah, Chul Ahn, Yisheng Fang, Nan Chen, Heather L. McArthur, Nicole Sinclair, Michael Yellin, Joyce O’Shaughnessy, Rita Nanda, Suzanne D. Conzen, Carlos L. Arteaga · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.2022.40.16_suppl.tps1126 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、Radiopharmaceutical Chemistry and Applications、HER2/EGFR in Cancer Research

TPS1126 Background: Only a subset of patients with metastatic triple-negative breast cancer demonstrate response to currently approved PD-1 immune checkpoint blockade, and few have durable responses. Antigen presentation defects may be a reason for this low response because deficiency of antigen-presenting DC1 dendritic cells is associated with poor anti-tumor immunity. CD40 agonists are a class of agents that activate antigen presenting cells including dendritic cells and B cells and also repolarize macrophages. Flt3 ligand is a growth factor that increases dendritic cells. In line with this, we recently demonstrated in pre-clinical models that the combination of liposomal-doxorubicin chemotherapy, a CD40 agonist, and a Flt3 ligand improves outcomes of breast cancer compared to alternate combinations. Methods: This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic triple-negative breast cancer. Patients will be randomized to 3 lead-in arms (triplet therapy, doublet immunotherapy only, liposomal-doxorubicin only) prior to receiving full triplet therapy with fresh tissue biopsies before and after the lead-in treatment. CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Primary endpoint is determination of a recommended...