Abstract OT2-17-01: Phase 1 trial of anthracycline 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, Nisha Unni, Namrata Peswani, Dawn Klemow, Samira Syed, Shahbano Shakeel, Farjana Fattah, Chul Ahn, Yisheng Fang, Heather L. McArthur, Nicole Sinclair, Michael Yellin, Denise A. Yardley, Nan Chen, Joyce O’Shaughnessy, Rita Nanda, Suzanne D. Conzen, Carlos L. Arteaga · 发表于：Cancer Research · 年份：2023 · DOI：10.1158/1538-7445.sabcs22-ot2-17-01 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Advanced Breast Cancer Therapies、Radiopharmaceutical Chemistry and Applications

Abstract Background: Only a subset of patients with metastatic triple-negative breast cancers (TNBC) demonstrate response to FDA approved PD-1 immune checkpoint blockade (ICB), and few have durable responses. Data suggests that breast cancers have defects in antigen presentation and that antigen presenting cells especially the DC1 subtype of dendritic cells (DCs) are required for response to ICB. CD40 agonists activate antigen presenting cells including DCs and B cells and also 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 TNBC models that the combination of liposomal-doxorubicin chemotherapy, a CD40 agonist, and a Flt3 ligand improves outcomes 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 TNBC. Patients will be randomized to 3 lead-in arms (triplet therapy, doublet immunotherapy only, or liposomal-doxorubicin only) for 1 cycle prior to receiving 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 phase 2 d...